Genes associated with canine osteoarthritis and related methods and compositions

ABSTRACT

Described herein is a combination containing polynucleotide molecules that are differentially expressed in osteoarthritis. Also described are methods that may be used for diagnosis and prognosis of osteoarthritis, as well as methods that may be used to screen test substances for effectiveness in treatment modalities for osteoarthritis. Also described are devices and kits that may be used with the described methods.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit of U.S. Application No. 60/541,346, filed Feb. 2, 2004, the disclosure of which is hereby incorporated by reference in its entirety.

REFERENCE TO SEQUENCE LISTING ON COMPACT DISK

This disclosure includes a Sequence Listing submitted under §1.821(c) on compact disc. The compact disc, created Jun. 18, 2007, is entitled “NEST 0021” and contains one Sequence Listing filed in ASCII text format, in accordance with 37 C.F.R. 1.821(c). The Sequence Listing file is entitled “NEST0021.5T25.txt”, and comprises SEQ ID NOs.:1 through 1611 in 692 kilobytes of disk space. The entire contents of the compact disc, the NEST0021.5T25.txt, and each of SEQ ID NOs:1 through 1611, are incorporated herein by reference.

FIELD OF THE INVENTION

This invention relates to the field of degenerative joint diseases, such as osteoarthritis. More particularly, the invention relates to novel compositions, devices and methods based on unique profiles of gene expression associated with osteoarthritis.

BACKGROUND OF THE INVENTION

Osteoarthritis (OA), also commonly referred to as degenerative joint disease, is recognized in humans and all veterinary species (Richardson et al., (1997) Vet. Clin. North Am. 27:883-911). OA is a prevalent and debilitating disease in canines and is often associated with hip dysplasia (Martinez, S. (1997) Osteoarthritis, Vet. Clinics of N. Am.: Small Animal Practice 27 (4):735-758.). There is a high degree of similarity between canine and human osteoarthritis, thus making it an excellent animal model for the study of human osteoarthritis. While causative factors remain largely unknown, the disease is characterized by the imbalance of cartilage matrix degradation outweighing cartilage matrix synthesis. Chondrocyte apoptosis and inflammation may also be associated with the disease (Pelletier, J., et al. (2001) Arthritis & Rheumatism 44 (6):1237-1247; Lotz, M. (1999) Osteoarthritis and Cartilage 7: 389-391).

The disease is typically slow in progression and characterized by degeneration of articular cartilage with a loss of both proteoglycan and collagen and by proliferation of new bone. In addition, an inflammatory response can occur within the synovial membrane. Canine osteoarthritis can arise as a secondary condition resulting, in particular, from hip displasia or from osteochondritis dissecans (Martinez, supra). Acquired conditions involving traumatic events can also lead to osteoarthritis in the dog (Martinez et al., Vet. Clin. North Am. 27:759-775, 1997). Treatment modalities for osteoarthritis can include the administration of anti-inflammatory drugs as well as the manipulation of dietary fatty acids (Richardson et al., supra).

Diagnosis of canine osteoarthritis is typically based upon symptomotology. Dogs having osteoarthritis show a lameness which may have a gradual onset but can flare up acutely after exercise. The lameness is exacerbated by rest but decreases after a few minutes of activity. Cold damp conditions, obesity and prolonged exercise often worsen signs of lameness (Pederson et al, in Textbook of Veterinary Internal Medicine, 5th Ed., Ettinger et al., ed., W.B. Saunders and Co., Philadelphia, 2000, pp. 1862-1886).

With the emergence of the genomic sciences, it has become apparent that not only is the regulation of gene expression intimately involved in normal homeostasis, alterations in the differential expression of genes is one aspect in the development of diseases. As a result, the evaluation of gene expression patterns in disease has become increasingly recognized as being crucial to the understanding of disease processes at the molecular level. (Going et al., European J. Cancer 35:1895-1904, 1999; Wang et al., Cardiovasc. Res. 35:414-421). A number of approaches have emerged for studying comparative gene expression and the current emphasis has been on high throughput analysis methods. (for review see Carulli et al, J. Cell. Biochem. Suppl. 30/32:286-296, 1998; Kozian et al., Trends Biotechnol 17:73-78, 1999). Recent methods developed for high throughput analysis of differential gene expression include, for example, EST sequencing (Adams et al., Science 252:1651-1656, 1991; Adams et al., Nature 377:3-16, 1995), microarray hybridization (Schena et al., Science 270:467-470, 1995), and differential display (Liang et al., Science 257:967-970, 1992; Welsh et al., Nucleic Acids Res. 20:4965-4970, 1992).

Gene expression in osteoarthritis, and particularly in canine osteoarthritis, has not been comprehensively studied. Accordingly, a need exists to identify nucleic acid sequences and their encoded proteins which are differentially expressed in osteoarthritis. This information would be useful to diagnose the osteoarthritic disease state, or pre-disposition to the disease, in a subject, as well as to identify substances useful in the treatment or prevention of osteoarthritis.

SUMMARY OF THE INVENTION

In accordance with an aspect of the present invention, a number of polynucleotides comprising at least a fragment of a gene have been identified as being differentially expressed in osteoarthritic or pre-osteoarthritic subjects, compared to expression in subjects which are not osteoarthritic or pre-osteoarthritic.

In accordance with an aspect of the present invention, differentially expressed genes, gene fragments, and encoded gene products, as well as the expression patterns associated with the group of genes, are used to advantage in a number of methods for the detection of changes in gene expression associated with osteoarthritis, particularly canine osteoarthritis. Additional aspects of the invention relate to methods for the identification of agents useful in treating and/or preventing osteoarthritis.

In accordance with additional aspects of the present invention, compositions, devices and test kits are provided to facilitate the practice of methods provided according to certain embodiments of the invention.

Other features and advantages of the present invention will be understood by reference to the detailed description and the examples that follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows representative gels used in differential display analysis of canine osteoarthritis. A. Differential display of osteoarthritic vs. normal transcripts loaded in duplicate prior to band excision (D=osteoarthritic (Diseased), N=Normal). B. The same gel after band excision.

FIG. 2 shows quantitative PCR analysis (qPCR) for selected OA-associated transcripts in canine cartilage. RNA expression is shown in arbitrary units. (OA AVG=average expression for osteoarthritic cartilage; C AVG=average expression in normal control).

TABLE 1 Correlation of Gene ID Numbers with Sequence ID Numbers. Gene SEQ Gene Gene Gene ID ID ID SEQ ID ID SEQ ID ID SEQ ID 1028c 1 768a 2 141c 3 1548c 4 1357a 5 168c 6 383d 7 2127c 8 530b 9 1405c 10 1765a 11 166a 12 1797a 13 1729a 14 1857c 15 523a 16 2172c 17 58a 18 244a 19 70d 20 1472a 21 452a 22 1481c 23 1940e 24 1930a 25 739a 26 1612a 27 14a 28 1727a 29 1220b 30 33a 31 1146a 32 1738b 33 810a 34 1993b 35 2147a 36 1678a 37 56a 38 1814c 39 129b 40 1924a 41 557b 42 1254a 43 1292c 44 2221c 45 490c 46 907a 47 469d 48 713a 49 1372a 50 482a 51 1098a 52 1785a 53 1624b 54 1441d 55 553b 56 2179a 57 1257b 58 1506d 59 1939c 60 2007a 61 13a 62 1288a 63 1949a 64 142.2c 65 1054a 66 1404c 67 8a 68 46a 69 1985a 70 326e 71 85.1c 72 1675a 73 574a 74 2159b 75 2108b 76 45.1b 77 2173a 78 1676a 79 581a 80 1695a 81 1414b 82 151b 83 112d 84 461a 85 1615b 86 310h 87 297a 88 1801b 89 23a 90 1739a 91 170a 92 1955a 93 2088a 94 2243b 95 1440a 96 2351c 97 1415b 98 2074b 99 2250a 100 1740a 101 81a 102 1248b 103 82b 104 1147a 105 12a 106 2201a 107 2266b 108 795a 109 206a 110 327f 111 212a 112 2083e 113 555b 114 1296a 115 272d 116 1709a 117 1945a 118 1631d 119 24a 120 1284a 121 184a 122 936b 123 1a 124 1677b 125 747a 126 737a 127 2166a 128 479c 129 2040d 130 1502a 131 72a 132 1917f 133 1650a 134 1620a 135 1951a 136 2355c 137 1394b 138 2071a 139 340a 140 368b 141 736a 142 17a 143 1475a 144 143.2c 145 1540a 146 1521b 147 2156c 148 2035d 149 1919a 150 1648a 151 1241a 152 1713a 153 144.2a 154 2255a 155 690a 156 2163a 157 979a 158 1747a 159 507a 160 890a 161 395a 162 1309b 163 1462a 164 1086c 165 1313a 166 1439b 167 153b 168 1790a 169 961a 170 493a 171 1463a 172 172a 173 1454d 174 1143d 175 766b 176 1412b 177 1423b 178 850a 179 148a 180 1696a 181 1396b 182 2141a 183 1503c 184 639a 185 1682a 186 2153a 187 2241a 188 2263b 189 1438a 190 2059b 191 1646a 192 465b 193 990a 194 1488b 195 1452a 196 1270a 197 2142a 198 945a 199 1367a 200 2198b 201 1139a 202 1138a 203 1008a 204 552a 205 2374a 206 1532a 207 2118a 208 1366a 209 1262b 210 144.1c 211 21a 212 1246a 213 1253a 214 2224a 215 1015d 216 2252b 217 154a 218 718a 219 11b 220 363a 221 370a 222 1551a 223 376a 224 84.2c 225 380a 226 372a 227 2148a 228 1800a 229 1090d 230 60a 231 96e 232 2015e 233 128a 234 621b 235 1174d 236 947a 237 1964a 238 619b 239 2222b 240 1468c 241 1629a 242 174a 243 2085c 244 1461a 245 764b 246 731a 247 1051a 248 613a 249 531a 250 1471a 251 1381a 252 44c 253 1892a 254 76b 255 366a 256 994b 257 1954e 258 409a 259 2120a 260 638b 261 329d 262 1853a 263 2247a 264 1746a 265 1081a 266 2002c 267 785b 268 1092b 269 1784a 270 1511b 271 1812b 272 1885c 273 1619a 274 2344a 275 1477a 276 360a 277 568a 278 1109a 279 1282b 280 1276a 281 1728a 282 1923b 283 2020b 284 556b 285 1711a 286 49a 287 1271a 288 1497c 289 967b 290 1329a 291 464b 292 1490a 293 188b 294 178a 295 631b 296 1244b 297 758b 298 1807a 299 276a 300 204a 301 543a 302 1764a 303 711a 304 35c 305 1401c 306 3c 307 494a 308 1616a 309 1070b 310 1928a 311 597c 312 1505c 313 1941e 314 742a 315 1299c 316 1960a 317 1191a 318 562a 319 2223a 320 2099a 321 342a 322 1347b 323 738b 324 1744a 325 1918a 326 1060a 327 1224b 328 861c 329 2033a 330 1349b 331 715a 332 1621a 333 379a 334 570b 335 1504d 336 441a 337 1943a 338 1033c 339 1758a 340 1772a 341 1707c 342 1474a 343 1920a 344 34a 345 2205a 346 1712a 347 1010a 348 1382d 349 269b 350 1972a 351 1298a 352 567b 353 949c 354 1545b 355 472a 356 1557a 357 489c 358 1495a 359 1302a 360 18a 361 182a 362 991b 363 1513b 364 992a 365 1032d 366 1373a 367 1400a 368 226a 369 1354a 370 1953a 371 794a 372 1604a 373 1245b 374 192a 375 1398a 376 1651a 377 64.2a 378 2161c 379 1618b 380 1516a 381 1803a 382 1593b 383 2109a 384 392a 385 1533a 386 1317a 387 1137b 388 51a 389 1708a 390 862c 391 1371a 392 2117b 393 1818a 394 851d 395 2113a 396 99b 397 92c 398 91f 399 90c 400 86.2d 401 86.1d 402 83d 403 80.1b 404 7a 405 78e 406 74c 407 73b 408 6b 409 68a 410 67a 411 66a 412 65.2a 413 63a 414 62c 415 59a 416 57a 417 55a 418 52a 419 50.1c 420 4a 421 43a 422 38a 423 37c 424 35b 425 2b 426 29a 427 27a 428 26a 429 25a 430 22b 431 20a 432 19c 433 16b 434 15b 435 10c 436 102a 437 103a 438 104a 439 106a 440 111a 441 120a 442 121b 443 122c 444 123c 445 124a 446 126a 447 130b 448 131a 449 132a 450 134b 451 135a 452 136b 453 142.1c 454 145b 455 146b 456 147b 457 150a 458 152b 459 157b 460 158a 461 159a 462 161b 463 162b 464 164c 465 165a 466 173a 467 175a 468 176a 469 177b 470 179b 471 180a 472 183a 473 185a 474 186a 475 187b 476 189a 477 190b 478 191a 479 195a 480 196a 481 197b 482 127b 483 105e 484 107.1a 485 107.2a 486 108a 487 109a 488 117.1d 489 117.2b 490 137b 491 140b 492 194a 493 181d 494 198e 495 199d 496 200a 497 201a 498 202a 499 203a 500 205a 501 208c 502 209a 503 210a 504 211b 505 214a 506 215a 507 216a 508 217b 509 218e 510 219g 511 220d 512 221b 513 222b 514 223a 515 224a 516 225a 517 227a 518 228a 519 229a 520 230a 521 231a 522 232a 523 233b 524 234a 525 235a 526 236a 527 237c 528 238a 529 239a 530 240a 531 241a 532 242a 533 243a 534 245a 535 246a 536 247a 537 248a 538 249a 539 250a 540 251a 541 252a 542 253b 543 254a 544 255a 545 257a 546 258a 547 260c 548 261c 549 262c 550 263b 551 266d 552 267d 553 268b 554 270b 555 273a 556 274b 557 275b 558 277a 559 278a 560 280c 561 282d 562 283a 563 284b 564 285b 565 286a 566 289a 567 291a 568 292b 569 294a 570 295a 571 296a 572 299a 573 301b 574 302a 575 499a 576 498a 577 497a 578 496c 579 495a 580 491a 581 359a 582 351b 583 344a 584 343b 585 338a 586 337c 587 336a 588 335a 589 334a 590 328b 591 325b 592 324a 593 312a 594 311c 595 309a 596 308c 597 307b 598 306b 599 303a 600 300b 601 163a 602 573b 603 561b 604 560b 605 559c 606 554c 607 551b 608 549a 609 542a 610 540a 611 539a 612 538a 613 537c 614 536a 615 535a 616 534b 617 533b 618 527a 619 526a 620 521b 621 520a 622 519a 623 517c 624 516c 625 515a 626 514a 627 513a 628 512b 629 509b 630 508a 631 505b 632 504a 633 503a 634 502a 635 501b 636 500a 637 345b 638 362b 639 364a 640 367a 641 369a 642 371a 643 374a 644 377b 645 378a 646 381a 647 386b 648 389c 649 390a 650 391a 651 393b 652 397b 653 455c 654 456c 655 457c 656 458b 657 459a 658 462b 659 466b 660 474a 661 478a 662 480a 663 483a 664 484a 665 485f 666 486a 667 487a 668 488a 669 545a 670 548c 671 558a 672 571a 673 572b 674 578c 675 579a 676 582c 677 584b 678 587b 679 590a 680 595a 681 684a 682 685a 683 686b 684 687a 685 688a 686 691a 687 692a 688 695a 689 696a 690 697a 691 698a 692 699a 693 700a 694 701a 695 702a 696 704b 697 706b 698 708a 699 709a 700 710a 701 712a 702 714a 703 716b 704 717b 705 719a 706 720a 707 722b 708 723a 709 724a 710 725a 711 727a 712 728b 713 730b 714 732a 715 733a 716 734a 717 740b 718 741b 719 743a 720 744a 721 745a 722 748a 723 749a 724 752a 725 753b 726 754d 727 757a 728 759b 729 761a 730 762a 731 763d 732 765a 733 770b 734 773a 735 774a 736 775a 737 780a 738 781a 739 783a 740 784a 741 786a 742 787b 743 788a 744 789a 745 791b 746 792a 747 797a 748 798a 749 799a 750 969a 751 968a 752 966a 753 964a 754 963c 755 959a 756 957c 757 956d 758 953a 759 952a 760 946a 761 944d 762 943b 763 942b 764 939a 765 938b 766 935b 767 934b 768 931a 769 930a 770 928a 771 927a 772 926a 773 925a 774 923a 775 921c 776 919b 777 918a 778 916c 779 915a 780 914a 781 913a 782 912b 783 911a 784 910c 785 909a 786 906a 787 905a 788 904a 789 902a 790 900a 791 899a 792 896b 793 894b 794 893a 795 891a 796 885a 797 883c 798 843a 799 841b 800 839a 801 838b 802 837c 803 836a 804 834b 805 833a 806 832a 807 831a 808 828a 809 826b 810 824b 811 823a 812 821a 813 820a 814 817a 815 816a 816 815a 817 813a 818 811a 819 808b 820 1633a 821 1632a 822 1627a 823 1625b 824 1614b 825 1613b 826 1607a 827 1605b 828 1544b 829 1526a 830 1524a 831 1522b 832 1520a 833 1519a 834 1518a 835 1514a 836 1512a 837 1508b 838 1507a 839 1493a 840 1492a 841 1487b 842 1486d 843 1482a 844 1480a 845 1476a 846 1469a 847 1466b 848 1460a 849 1459c 850 1422a 851 1418a 852 1409b 853 1407a 854 1406a 855 1402b 856 1399a 857 1397b 858 1369c 859 1364d 860 1325b 861 1324a 862 1321a 863 1318a 864 1316b 865 1312a 866 1301a 867 1289a 868 1285a 869 1277a 870 1273b 871 1272a 872 1269b 873 1267a 874 1266a 875 1263b 876 1251a 877 1195a 878 1194a 879 1193b 880 1192b 881 1189a 882 1188b 883 1185a 884 1184a 885 1183a 886 1182a 887 1178a 888 1175a 889 1172a 890 1171a 891 1170a 892 1167b 893 1166b 894 1132a 895 1126b 896 1117a 897 1111b 898 1104b 899 1103a 900 1101a 901 1048c 902 1023c 903 1014d 904 1009c 905 1239b 906 1240a 907 1243a 908 1368a 909 1370a 910 1383a 911 408a 912 415b 913 421a 914 443b 915 863c 916 864c 917 867d 918 870e 919 874e 920 881c 921 940a 922 941a 923 958a 924 975a 925 980b 926 981a 927 987a 928 993b 929 996a 930 1012a 931 1013a 932 1018a 933 1019a 934 1020a 935 1022a 936 1026b 937 1029a 938 1031a 939 1034a 940 1036a 941 1057b 942 1177c 943 1252a 944 1255a 945 1264c 946 1274c 947 1275c 948 1279c 949 1281c 950 1286d 951 1287c 952 1290d 953 1310a 954 1424a 955 1426a 956 1427a 957 1428a 958 1430a 959 1431a 960 1432a 961 1435a 962 1436b 963 1437c 964 1444b 965 1445b 966 1446a 967 1447a 968 1448a 969 1451a 970 1455c 971 1542c 972 1549a 973 1611a 974 1639a 975 1641b 976 1152d 977 1158c 978 1159b 979 1163d 980 1420c 981 1771b 982 1859a 983 1861a 984 1886a 985 1889a 986 1900b 987 1905a 988 2110a 989 2129a 990 2137b 991 2143a 992 2225b 993 2234a 994 2237b 995 2238a 996 2239b 997 2248a 998 2267a 999 436c 1000 446f 1001 524a 1002 525f 1003 529b 1004 541b 1005 547c 1006 563a 1007 564a 1008 565a 1009 566a 1010 575b 1011 589a 1012 591a 1013 609a 1014 610a 1015 611a 1016 612b 1017 614a 1018 617a 1019 620a 1020 622a 1021 623a 1022 624b 1023 625a 1024 626a 1025 629a 1026 630a 1027 632a 1028 633a 1029 634a 1030 637c 1031 640b 1032 641a 1033 642a 1034 825d 1035 846a 1036 847a 1037 852a 1038 948a 1039 1242a 1040 1634a 1041 2138a 1042 2233a 1043 615a 1044 618b 1045 628a 1046 636a 1047 835c 1048 2122a 1049 1050a 1050 1110b 1051 1228a 1052 1655a 1053 1659a 1054 1673b 1055 1694b 1056 1703b 1057 1704b 1058 1714a 1059 1717a 1060 1718a 1061 1719a 1062 1720a 1063 1721a 1064 1722a 1065 1724a 1066 1726a 1067 1730a 1068 1731a 1069 1748b 1070 1749a 1071 1750a 1072 1751a 1073 1816a 1074 1880a 1075 1884a 1076 1887a 1077 1895b 1078 1903a 1079 1912a 1080 1914b 1081 1921a 1082 1967a 1083 1968a 1084 1977a 1085 1979a 1086 1981a 1087 1982a 1088 1986b 1089 1987a 1090 1988a 1091 1990a 1092 1992b 1093 1994a 1094 2073b 1095 2075a 1096 2076c 1097 2078a 1098 2086a 1099 2092c 1100 2093a 1101 2094a 1102 2097a 1103 2100b 1104 2104a 1105 2105a 1106 2106a 1107 2111b 1108 2119a 1109 2126b 1110 2128a 1111 2132a 1112 2135d 1113 2136b 1114 2145c 1115 2149d 1116 2150a 1117 2154a 1118 2158c 1119 2160a 1120 2162b 1121 2167a 1122 2170a 1123 2171c 1124 2174a 1125 2178c 1126 2182b 1127 388a 1128 445e 1129 856c 1130 1216a 1131 1705a 1132 1725a 1133 1734b 1134 1781a 1135 1782b 1136 1789a 1137 1791b 1138 1792a 1139 1794a 1140 1795a 1141 1796a 1142 1817a 1143 1897b 1144 1971b 1145 2095a 1146 2144a 1147 2146a 1148 384c 1149 600e 1150 878c 1151 1011a 1152 1021a 1153 1025a 1154 1037c 1155 1039c 1156 1040b 1157 1058a 1158 1059a 1159 1061a 1160 1062a 1161 1063b 1162 1064a 1163 1068a 1164 1069a 1165 1071b 1166 1072a 1167 1073a 1168 1121a 1169 1122b 1170 1130a 1171 1134a 1172 1135a 1173 1136b 1174 1176a 1175 1180a 1176 1190b 1177 1204a 1178 1208a 1179 1215b 1180 1217a 1181 1227b 1182 1236a 1183 1249a 1184 1297a 1185 1308c 1186 1314a 1187 1355a 1188 1361a 1189 1363b 1190 1386a 1191 1388a 1192 1390a 1193 1391a 1194 1417a 1195 1510a 1196 1536b 1197 1537c 1198 1546b 1199 1547c 1200 1552a 1201 1554c 1202 1556a 1203 1558c 1204 1591a 1205 1592a 1206 1594a 1207 1595b 1208 1596b 1209 1597a 1210 1598a 1211 1599a 1212 1600a 1213 1601a 1214 1602a 1215 1603a 1216 1609c 1217 1617a 1218 1626c 1219 1628a 1220 1637c 1221 1642a 1222 1657a 1223 1661a 1224 1662a 1225 1663a 1226 1665a 1227 1671b 1228 1672a 1229 1688c 1230 1691b 1231 1715a 1232 1735a 1233 1810a 1234 1856c 1235 1860a 1236 1874b 1237 1881b 1238 1901c 1239 1913a 1240 2204b 1241 2230a 1242 1035a 1243 1124a 1244 1294b 1245 1319a 1246 1411a 1247 1421a 1248 1588b 1249 1645a 1250 1667a 1251 1798a 1252 450a 1253 1076c 1254 1077a 1255 1085c 1256 1087c 1257 1093b 1258 1094b 1259 1102a 1260 1106a 1261 1108a 1262 1112a 1263 1116a 1264 1335b 1265 1336c 1266 1338a 1267 1339b 1268 1341a 1269 1449a 1270 1457b 1271 1458a 1272 1479a 1273 1485b 1274 1489a 1275 1499a 1276 1501a 1277 1509a 1278 1525a 1279 1531c 1280 1534b 1281 1535a 1282 1828b 1283 1834b 1284 1927a 1285 1929c 1286 1937c 1287 1942b 1288 1944a 1289 1946b 1290 1947a 1291 1948b 1292 1950a 1293 1952a 1294 1956a 1295 1958b 1296 2003a 1297 2021a 1298 2022a 1299 2023b 1300 2024a 1301 2029a 1302 2032b 1303 2053a 1304 2056d 1305 2065a 1306 2070a 1307 1334a 1308 1453a 1309 2066b 1310 1737b 1311 1741a 1312 1779b 1313 1891a 1314 1911b 1315 1922a 1316 1067a 1317 1091b 1318 1095a 1319 1105a 1320 1131b 1321 1169b 1322 1196b 1323 1213d 1324 1222a 1325 1229c 1326 1327a 1327 1346b 1328 1358b 1329 1384a 1330 1484b 1331 1500b 1332 1693b 1333 1752a 1334 1802a 1335 1871a 1336 85.2b 1337 2331c 1338 1687a 1339 1660d 1340 1654c 1341 1808a 1342 1425a 1343 1410b 1344 1378b 1345 1376a 1346 995a 1347 989a 1348 2258a 1349 2084c 1350 1250a 1351 1002b 1352 583e 1353 2229a 1354 1001a 1355 1002b 1356 1003a 1357 1004a 1358 1005a 1359 1006b 1360 1007a 1361 1042a 1362 1044c 1363 1045a 1364 1099c 1365 1120a 1366 1125a 1367 1212b 1368 1225b 1369 1226d 1370 1304a 1371 1322c 1372 1515c 1373 1527a 1374 1528b 1375 1539c 1376 1541a 1377 1561a 1378 1690a 1379 1692a 1380 1736b 1381 1763b 1382 1766a 1383 1777a 1384 1883b 1385 1888c 1386 1898a 1387 2043b 1388 2045d 1389 2130b 1390 2139a 1391 213a 1392 2140b 1393 2165a 1394 2199a 1395 2210a 1396 2254a 1397 2264b 1398 2268a 1399 265a 1400 365b 1401 492a 1402 550a 1403 635a 1404 726b 1405 750b 1406 772b 1407 776a 1408 777a 1409 793a 1410 800b 1411 801b 1412 803b 1413 804a 1414 806b 1415 827b 1416 855c 1417 877e 1418 880e 1419 932b 1420 933b 1421 984a 1422 986a 1423 988b 1424 989a 1425 997a 1426 1016b 1427 1027a 1428 1030a 1429 1038b 1430 1052b 1431 1053a 1432 1088c 1433 1089d 1434 1097c 1435 1145a 1436 1165d 1437 1260c 1438 1315c 1439 1348b 1440 1352b 1441 1360b 1442 1387b 1443 1403a 1444 1413b 1445 1416a 1446 1419a 1447 1442d-r 1448 1443a 1449 1450a 1450 1483a 1451 1562a 1452 1564a 1453 1565c 1454 1567a 1455 1568a 1456 1569b 1457 1570a 1458 1572a 1459 1573a 1460 1574b 1461 1575a 1462 1576a 1463 1577a 1464 1578a 1465 1579a 1466 1580b 1467 1581a 1468 1583a 1469 1584a 1470 1585b 1471 1586a 1472 1628d 1473 1630b 1474 1666d 1475 1669d 1476 1670d 1477 1755a 1478 1759b 1479 1760c 1480 1775a 1481 1778c 1482 1780a 1483 1809a 1484 1846d 1485 1849d 1486 1852a 1487 1863c 1488 1864b 1489 1865e 1490 1879a 1491 1894a 1492 1906a 1493 1961e 1494 1966a 1495 1989b 1496 1991d 1497 2008a 1498 2013a 1499 2014f 1500 2034a 1501 2036b 1502 2041d 1503 2042h 1504 2043b 1505 2044a 1506 2045d 1507 2046a 1508 2048a 1509 2101c 1510 2107b 1511 2124a-r 1512 2235a 1513 2240a 1514 2251d 1515 2271a 1516 2341b 1517 2356a 1518 2358b 1519 2371a 1520 2373a 1521 322a 1522 805a 1523 924a 1524 965a 1525 898a 1526 879c 1527 865e 1528 627b 1529 406a-r 1530 321a 1531 320a 1532 319b 1533 317a 1534 315a 1535 314a 1536 313a 1537 2249a 1538 2189b 1539 2134b 1540 2125a 1541 1811b 1542 1553b 1543 1393b 1544 1389b 1545 1377b 1546 1356a 1547 1353a 1548 1041a 1549 1635a 1550 1385b 1551 1365a 1552 50.2b 1553 48b 1554 440a 1555 413a 1556 2123a 1557 1323br 1558

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS Definitions

The following definitions are provided to facilitate an understanding of the present invention:

“Nucleic acid” or a “nucleic acid molecule” as used herein refers to any DNA or RNA molecule, either single or double stranded and, if single stranded, the molecule of its complementary sequence in either linear or circular form. In discussing nucleic acid molecules, a sequence or structure of a particular nucleic acid molecule may be described herein according to the normal convention of providing the sequence in the 5′ to 3′ direction. With reference to nucleic acids according to aspects of the invention, the term “isolated nucleic acid” is sometimes used. This term, when applied to DNA, refers to a DNA molecule that is separated from sequences with which it is immediately contiguous in the naturally occurring genome of the organism in which it originated. For example, an “isolated nucleic acid” may comprise a DNA molecule inserted into a vector, such as a plasmid or virus vector, or integrated into the genomic DNA of a prokaryotic or eukaryotic cell or host organism.

When applied to RNA, the term “isolated nucleic acid” refers primarily to an RNA molecule encoded by an isolated DNA molecule as defined above. Alternatively, the term may refer to an RNA molecule that has been sufficiently separated from other nucleic acids with which it would be associated in its natural state (i.e., in cells or tissues). An isolated nucleic acid (either DNA or RNA) may further represent a molecule produced directly by biological or synthetic means and separated from other components present, during its production.

The terms “percent similarity”, “percent identity” and “percent homology” when referring to a particular sequence are used as set forth in the University of Wisconsin GCG software program.

A “polynucleotide,” “polynucleotide molecule” or “polynucleotide sequence” refers to a chain of nucleotides. It may refer to a DNA or RNA molecule, either single or double stranded and, if single stranded, the molecule of its complementary sequence in either linear or circular form. Preferably, the chain has from about 50 to 10,000 nucleotides, more preferably from about 150 to 3,500 nucleotides. In some instances, the sequences will be fully complementary (no mismatches) when aligned. In other instances, there may be up to about a 30% mismatch in the sequences.

The term “oligonucleotide,” as used herein refers to sequences, primers and probes of the present invention, and is defined as a nucleic acid molecule comprised of two or more ribo or deoxyribonucleotides, preferably more than three. The exact size of the oligonucleotide will depend on various factors and on the particular application and use of the oligonucleotide.

A “fragment” refers to a nucleic acid sequence that is preferably at least about 10 nucleic acids in length, more preferably about 40 nucleic acids, and most preferably about 100 nucleic acids in length and encompasses, for example, fragments consisting of nucleic acids 1-100, 300-400, 500-600, 800-900 of SEQ ID NOs:1-1558 or fragments of similar length at the 3′ end of SEQ ID NOs:1-1558. A “fragment” can also mean a stretch of at least about 100 consecutive nucleotides that contains one or more deletions, insertions or substitutions. A “fragment” can also mean the whole coding sequence of a gene and may include 5′ and 3′ untranslated regions. A “fragment” can also refer to polypeptide sequences which are preferably at least about 5 to about 15 amino acids in length, most preferably at least about 10 amino acids long, and which retain some biological activity or immunological activity of a sequence.

The term “gene” or “genes” refers to the partial or complete coding sequence of a gene. The term also refers to 5′ or 3′ untranslated regions of a transcript. The phrase “gene differentially expressed in osteoarthritis” refers to a gene whose amount of mRNA expressed from that gene or the amount of gene product translated from the mRNA is detectably different, i.e. either greater or lesser, in cells from subjects having osteoarthritis or in pre-osteoarthritic subjects compared to the amount of mRNA or translated gene product in cells from normal subjects which are neither osteoarthritic nor pre-osteoarthritic. As used herein, “pre-osteoarthritis” or “pre-osteoarthritic” is intended to mean that a subject is predisposed to developing osteoarthritis at a later date, but may not have any overt signs or symptoms of osteoarthritis. Preferably, the abundance of transcription or translation products of a differentially expressed gene derived from an osteoarthritic or pre-osteoarthritic sample differs by least about 1.15 fold, more preferably at least about 1.2 fold, more preferably at least about 1.3 fold, more preferably at least about 1.4 fold, more preferably at least about 1.5 fold, more preferably at least about 1.6 fold, more preferably at least about 1.75 fold, more preferably at least about 2 fold, more preferably at least about 3 fold, more preferably at least about 10 fold, more preferably at least about 20 fold than that in a normal sample. The phrase “gene differentially expressed in osteoarthritis” also refers to genes that are not detectable in the normal transcript profile but are preferably at levels of at least about 2 copies per cell, more preferably at least about 3 copies per cell, in the osteoarthritic or pre-osteoarthritic tissue transcript profile.

The terms “osteoarthritis (OA)-related” and “osteoarthritis (OA)-associated genes” refer to genes that are differentially expressed in osteoarthritis as defined herein.

As used herein, the terms “reporter,” “reporter system,” “reporter gene,” or “reporter gene product” refer to an operative genetic system in which a nucleic acid comprises a gene that encodes a product that when expressed produces a reporter signal that is a readily measurable, e.g., by biological assay, immunoassay, radioimmunoassay, or by calorimetric, fluorogenic, chemiluminescent or other methods. The nucleic acid may be either RNA or DNA, linear or circular, single or double stranded, antisense or sense polarity, and is operatively linked to the necessary control elements for the expression of the reporter gene product. The required control elements will vary according to the nature of the reporter system and whether the reporter gene is in the form of DNA or RNA, but may include, but not be limited to, such elements as promoters, enhancers, translational control sequences, poly A addition signals, transcriptional termination signals and the like.

The terms “transform,” “transfect,” “transduce,” refer to any method or means by which a nucleic acid is introduced into a cell or host organism and may be used interchangeably to convey the same meaning. Such methods include, but are not limited to, transfection, electroporation, microinjection, PEG-fusion and the like.

The term “functional” as used herein implies that the nucleic or amino acid sequence is functional for the recited assay or purpose.

The phrase “consisting essentially of” when referring to a particular nucleotide or amino acid means a sequence having the properties of a given SEQ ID NO. For example, when used in reference to an amino acid sequence, the phrase includes the sequence per se and molecular modifications that would not affect the basic and novel characteristics of the sequence.

A “vector” is a replicon, such as a plasmid, cosmid, bacmid, phage, artificial chromosome (BAC, YAC) or virus, into which another genetic sequence or element (either DNA or RNA) may be inserted so as to bring about the replication of the attached sequence or element. A “replicon” is any genetic element, for example, a plasmid, cosmid, bacmid, phage, artificial chromosome (BAC, YAC) or virus, that is capable of replication largely under its own control. A replicon may be either RNA or DNA and may be single or double stranded.

The term “probe” as used herein refers to either a probe for a nucleic acid or a probe for a protein. When used in connection with nucleic acids, a “probe” refers to an oligonucleotide, polynucleotide or nucleic acid, either RNA or DNA, whether occurring naturally as in a purified restriction enzyme digest or produced synthetically, which is capable of annealing with or specifically hybridizing to a nucleic acid with sequences complementary to the probe. A probe may be either single stranded or double stranded. The exact length of the probe will depend upon many factors, including temperature, source of probe and method of use. For example, for diagnostic applications, depending on the complexity of the target sequence, an oligonucleotide probe typically contains about 10-100, preferably about 15-50, more preferably about 15-25 nucleotides. In certain diagnostic applications, a polynucleotide probe preferably contains about 90-1150 nucleotides, more preferably about 300-600 nucleotides, more preferably about 300 nucleotides. The probes herein are selected to be “substantially” complementary to different strands of a particular target nucleic acid sequence. This means that the probes must be sufficiently complementary so as to be able to “specifically hybridize” or anneal with their respective target strands under a set of pre-determined conditions. Therefore, the probe sequence need not reflect the exact complementary sequence of the target. For example, a non complementary nucleotide fragment may be attached to the 5′ or 3′ end of the probe, with the remainder of the probe sequence being complementary to the target strand. Alternatively, non complementary bases or longer sequences can be interspersed into the probe, provided that the probe sequence has sufficient complementarity with the sequence of the target nucleic acid to anneal therewith specifically. When used in connection with a protein, a “probe” is a protein binding substance capable of specifically binding a particular protein or protein fragment to the substantial exclusion of other proteins or protein fragments. Such binding substances may be any molecule to which the protein or peptide specifically binds, including DNA (for DNA binding proteins), antibodies (as described in greater detail herein), cell membrane receptors, peptides, cofactors, lectins, sugars, polysaccharides, cells, cell membranes, organelles and organellar membranes.

“Array” refers to an ordered arrangement of at least two probes on a substrate. At least one of the probes represents a control or standard, and the other, a probe of diagnostic interest. The arrangement of from about two to about 40,000 probes on a substrate assures that the size and signal intensity of each labeled complex formed between a probe and a sample nucleic acid or protein binding substance is individually distinguishable.

A “hybridization complex” is formed between nucleic acid molecules of a sample when the purines of one molecule hydrogen bond with the pyrimidines of the complementary molecule, e.g., 5′-A-G-T-C-3′ base pairs with 3′-T-C-A-G-5′. The degree of complementarity and the use of nucleotide analogs affect the efficiency and stringency of hybridization reactions.

The term “specifically hybridize” refers to the association between two single stranded nucleic acid molecules of sufficiently complementary sequence to permit such hybridization under predetermined conditions generally used in the art (sometimes termed “substantially complementary”). For example, the term may refer to hybridization of a nucleic acid probe with a substantially complementary sequence contained within a single stranded DNA or RNA molecule according to an aspect of the invention, to the substantial exclusion of hybridization of the nucleic acid probe with single stranded nucleic acids of non-complementary sequence.

“Sample” is used in its broadest sense as containing nucleic acids, proteins, antibodies, and the like. A sample may comprise, for example, a bodily fluid; the soluble fraction of a cell preparation, or an aliquot of media in which cells were grown; a chromosome, an organelle, or membrane isolated or extracted from a cell; genomic DNA, RNA, or cDNA in solution or bound to a substrate; a cell; a tissue or a tissue biopsy; a tissue print; a fingerprint, buccal cells, skin, or hair; and the like.

A “standard” refers to a control sample that comprises material from a source in a normal (as opposed to OA-related) biological state. An OA-related biological state may include, for example, one in which the source has OA, is predisposed to develop OA, or exhibits certain biological characteristics of OA. For example, a standard sample may comprise nucleic acids or proteins from a normal subject that is not osteoarthritic or pre-osteoarthritic. Standard samples may also include samples from normal cells or tissue that have not been treated to elicit an immune response that may model certain aspects of OA.

“Specific binding” refers to a special and precise interaction between two molecules which is dependent upon their structure, particularly their molecular side groups. For example, the intercalation of a regulatory protein into the major groove of a DNA molecule, the hydrogen bonding along the backbone between two single stranded nucleic acids, or the binding between an epitope of a protein and an agonist, antagonist, or antibody.

The term “primer” as used herein refers to a nucleic acid molecule, either RNA or DNA, either single stranded or double stranded, either derived from a biological system, generated by restriction enzyme digestion, or produced synthetically which, when placed in the proper environment, is able to functionally act as an initiator of template-dependent nucleic acid synthesis. When presented with an appropriate nucleic acid template, suitable nucleoside triphosphate precursors of nucleic acids, a polymerase enzyme, suitable cofactors and conditions such as appropriate temperature and pH, the primer may be extended at its 3′ terminus by the addition of nucleotides by the action of a polymerase or similar activity to yield an primer extension product. The primer may vary in length depending on the particular conditions and requirement of the application. For example, in diagnostic applications according to particular embodiments of the invention, a primer may be an oligonucleotide primer, preferably about 15-25 or more nucleotides in length. The primer must be of sufficient complementarity to the desired template to prime the synthesis of the desired extension product, that is, to be able anneal with the desired template strand in a manner sufficient to provide the 3′ hydroxyl moiety of the primer in appropriate juxtaposition for use in the initiation of synthesis by a polymerase or similar enzyme. It is not required that the primer sequence represent an exact complement of the desired template. For example, a non complementary nucleotide sequence may be attached to the 5′ end of an otherwise complementary primer. Alternatively, non complementary bases may be interspersed within the oligonucleotide primer sequence, provided that the primer sequence has sufficient complementarity with the sequence of the desired template strand to functionally provide a template primer complex for the synthesis of the extension product.

Amino acid residues described herein are preferred to be in the “L” isomeric form. However, residues in the “D” isomeric form may be substituted for any L amino acid residue, provided the desired properties of the polypeptide are retained. All amino acid residue sequences represented herein conform to the conventional left-to-right amino terminus to carboxy terminus orientation.

A “fragment” or “portion” of a polypeptide means a stretch of amino acid residues of at least about five to seven contiguous amino acids, often at least about seven to nine contiguous amino acids, typically at least about nine to thirteen contiguous amino acids and, most preferably, at least about twenty to thirty or more contiguous amino acids. Fragments of the polypeptide sequence, antigenic determinants, or epitopes are useful for eliciting immune responses to a portion of the protein amino acid sequence.

Different “variants” of the differentially expressed polypeptides exist in nature. These variants may be alleles characterized by differences in the nucleotide sequences of the gene coding for the protein, or may involve different RNA processing or post translational modifications. The skilled person can produce variants having single or multiple amino acid substitutions, deletions, additions or replacements. These variants may include, inter alia: (a) variants in which one or more amino acids residues are substituted with conservative or non conservative amino acids, (b) variants in which one or more amino acids are added to the polypeptide, (c) variants in which one or more amino acids include a substituent group, and (d) variants in which the polypeptide is fused with another peptide or polypeptide such as a fusion partner, a protein tag or other chemical moiety, that may confer useful properties to the polypeptide, such as, for example, an epitope for an antibody, a polyhistidine sequence, a biotin moiety and the like. Other polypeptides of the invention may include variants in which amino acid residues from one species are substituted for the corresponding residue in another species, either at the conserved or non conserved positions. In another embodiment, amino acid residues at non conserved positions are substituted with conservative or non conservative residues. The techniques for obtaining these variants, including genetic (suppressions, deletions, mutations, etc.), chemical, and enzymatic techniques are known to the person having ordinary skill in the art. To the extent such allelic variations, analogues, fragments, derivatives, mutants, and modifications, including alternative nucleic acid processing forms and alternative post translational modification forms result in derivatives of the differentially expressed polypeptide that retain any of the biological properties of the differentially expressed polypeptide, they are included within the scope of this invention.

The term “isolated protein” or “isolated and purified protein” refers primarily to a protein produced by expression of an isolated nucleic acid molecule according to an aspect the invention. Alternatively, this term may refer to a protein that has been sufficiently separated from other proteins with which it would naturally be associated, so as to exist in “substantially pure” form. “Isolated” is not meant to exclude artificial or synthetic mixtures with other compounds or materials, or the presence of impurities that do not interfere with the fundamental activity, and that may be present, for example, due to incomplete purification, addition of stabilizers, or compounding into, for example, immunogenic preparations or pharmaceutically acceptable preparations.

The term “substantially pure” refers to a preparation comprising at least about 50-60% by weight of a given material (e.g., nucleic acid, protein, etc.). More preferably, the preparation comprises at least about 75% by weight, and most preferably about 90-95% by weight of the given compound. Purity is measured by methods appropriate for the given material (e.g. chromatographic methods, agarose or polyacrylamide gel electrophoresis, HPLC analysis, and the like).

The term “tag,” “tag sequence” or “protein tag” refers to a chemical moiety, either a nucleotide, oligonucleotide, polynucleotide or an amino acid, peptide or protein or other chemical, that when added to another sequence, provides additional utility or confers useful properties, particularly in the detection or isolation, of that sequence. Thus, for example, a homopolymer nucleic acid sequence or a nucleic acid sequence complementary to a capture oligonucleotide may be added to a primer or probe sequence to facilitate the subsequent isolation of an extension product or hybridized product. In the case of protein tags, histidine residues (e.g., 4 to 8 consecutive histidine residues) may be added to either the amino or carboxy terminus of a protein to facilitate protein isolation by chelating metal chromatography. Alternatively, amino acid sequences, peptides, proteins or fusion partners representing epitopes or binding determinants reactive with specific antibody molecules or other molecules (e.g., flag epitope, c myc epitope, transmembrane epitope of the influenza A virus hemagglutinin protein, protein A, cellulose binding domain, calmodulin binding protein, maltose binding protein, chitin binding domain, glutathione S transferase, and the like) may be added to proteins to facilitate protein isolation by procedures such as affinity or immunoaffinity chromatography. Chemical tag moieties include such molecules as biotin, which may be added to either nucleic acids or proteins and facilitates isolation or detection by interaction with avidin reagents, and the like. Numerous other tag moieties are known to, and can be envisioned by, the trained artisan, and are contemplated to be within the scope of this definition.

An “antibody” or “antibody molecule” is any immunoglobulin, including antibodies and fragments thereof, that binds to a specific antigen. The term includes polyclonal, monoclonal, chimeric, and bispecific antibodies. As used herein, antibody or antibody molecule contemplates both an intact immunoglobulin molecule and an immunologically active portion of an immunoglobulin molecule such as those portions known in the art as Fab, Fab′, F(ab′)2 and F(v).

As used herein, the term “subject” or “patient” refers to both humans and animals, unless specified that the “subject” or “patient” is an animal or a human. Animal subjects are preferably vertebrates, and more preferably, mammals.

“Therapeutic modality” refers to any means of treating and/or preventing a disease, condition or disorder.

In one aspect of the present invention, a number of genes have been identified that are differentially expressed in osteoarthritic subjects as compared to non-osteoarthritic subjects. These genes and gene fragments, as well as their encoded proteins and fragments, may be used, for example, in a variety of diagnostic and prognostic assays, as well as assays useful in screening test substances for effectiveness in treatment modalities for osteoarthritis.

In certain embodiments of the invention, expression of at least one differentially expressed gene may be measured. In preferred embodiments, expression of two or more differentially expressed genes may be measured, providing a gene expression pattern or gene expression profile. More preferably, measurement of a multiplicity of differentially expressed genes may be performed, providing additional information for a gene expression pattern or profile.

In various embodiments of the present invention, changes in gene expression may be measured in one or both of two ways: (1) measuring transcription through detection of mRNA produced by a particular gene; and (2) measuring translation through detection of protein produced by a particular transcript.

Decreased or increased expression can be measured at the RNA level using any of the methods well known in the art for the quantitation of polynucleotides, such as, for example, PCR (including, without limitation, RT-PCR and qPCR), RNase protection, Northern blotting and other hybridization methods. The genes that are assayed or interrogated according to the present invention are typically in the form of mRNA or reverse transcribed mRNA. The genes may be cloned and/or amplified. The cloning itself does not appear to bias the representation of genes within a population. However, it may be preferable to use polyA+ RNA as a source, as it can be used with fewer processing steps.

In accordance with aspects of the present invention, 1558 genes have been identified whose functions are closely associated with osteoarthritis (OA). The association is determined by comparing expression of the genes in normal tissue and tissue from subjects diagnosed with OA. The genes so identified fall into two broad categories. The first category comprises known genes, many of whose association with OA had heretofore been unappreciated. These genes are listed in Table 6, along with their corresponding gene ID numbers and SEQ ID NOs.

According to another aspect of the invention, a second category comprises nucleic acid segments that do not demonstrate homology to previously identified sequences. Thus, this category is believed to include one or more novel genes. One preferred embodiment of the invention relates to an isolated nucleic acid molecule comprising a novel OA-associated gene, mRNA or cDNA produced from the OA-associated gene.

One aspect of the present invention relates to a combination of 1558 polynucleotide molecules that are differentially expressed in an osteoarthritic subject or in a pre-osteoarthritic subject compared to expression in subjects which are not osteoarthritic or pre-osteoarthritic. In one embodiment of the invention described herein, segments of 1558 OA-related genes from canine cartilage were obtained by employing differential display. The nucleotide sequences of these polynucleotides are set forth herein as SEQ ID NOs:1-1558 (Table 1 shows the correlation between SEQ ID NO. and Gene ID Number). BLAST analysis of these sequences identified homologies with of a number of nucleic acid sequences previously identified (Table 2) These include a number of previously identified nucleic acid sequences with no identified homologies to known genes. BLAST analysis also identified sequences showing homology to previously-identified genes; information including names of genes as well as database accession numbers for respective homologs of these is provided in Tables 2A and 2B.

TABLE 2A CaMax Ensemble Chrom Chrom Gene ID Ensemble Gene ID Transcript ID Description No. Loc. CaMax: 1002b CaMax: 1002b CaMax: ENSG00000138709 ENST00000264584 4 q28.2 1005a ENST00000326703 ENST00000326639 CaMax: ENSG00000152518 ENST00000282388 BUTYRATE RESPONSE 2 p21 1006b FACTOR 2 (TIS11D PROTEIN) (EGF-RESPONSE FACTOR 2) (ERF-2). [Source: SWISSPROT; Acc: P47974] CaMax: ENSG00000152518 ENST00000282388 BUTYRATE RESPONSE 2 p21 1007a FACTOR 2 (TIS11D PROTEIN) (EGF-RESPONSE FACTOR 2) (ERF-2). [Source: SWISSPROT; Acc: P47974] CaMax: 1008a CaMax: 1008a CaMax: ENSG00000122912 ENST00000265870 GRAVE'S DISEASE 10 q21.3 1009c CARRIER PROTEIN (GDC) (GRAVE'S DISEASE AUTOANTIGEN) (GDA) (MITOCHONDRIAL SOLUTE CARRIER PROTEIN HOMOLOG). [Source: SWISSPROT; Acc: P16260] CaMax: 1011a CaMax: 1011a CaMax: 1013a CaMax: ENSG00000109775 ENST00000264689 4 q35.1 1015d CaMax: 1016b CaMax: ENSG00000160961 ENST00000292530 ZINC FINGER PROTEIN 333. 19 p13.12 1019a [Source: SWISSPROT; Acc: Q96JL9] CaMax: ENSG00000064989 ENST00000264152 CALCITONIN GENE- 2 q32.1 1020a RELATED PEPTIDE TYPE 1 RECEPTOR PRECURSOR (CGRP TYPE 1 RECEPTOR). [Source: SWISSPROT; Acc: Q16602] CaMax: 1026b CaMax: 1026b CaMax: 1028c CaMax: 1028c CaMax: ENSG00000171567 ENST00000304782 TIGGER TRANSPOSABLE 2 q37.1 1029a ELEMENT DERIVED 1; JERKY (MOUSE) HOMOLOG-LIKE. [Source: RefSeq; Acc: NM_145702] CaMax: 103a CaMax: ENSG00000041880 ENST00000045065 POLY [ADP-RIBOSE] 3 p21.2 1044c POLYMERASE-3 (EC 2.4.2.30) (PARP-3) (NAD(+) ADP- RIBOSYLTRANSFERASE-3) (POLY[ADP-RIBOSE] SYNTHETASE-3) (PADPRT- 3) (HPARP-3) (IRT1). [Source: SWISSPROT; Acc: Q9Y6F1] CaMax: ENSG00000169045 ENST00000326748 HETEROGENEOUS 5 q35.3 104a ENST00000329433 NUCLEAR RIBONUCLEOPROTEIN H (HNRNP H). [Source: SWISSPROT; Acc: P31943] CaMax: 1050a CaMax: 1054a CaMax: 1057b CaMax: 1060a CaMax: ENSG00000138336 ENST00000260906 LEUKEMIA-ASSOCIATED 10 q21.3 1061a PROTEIN WITH A CXXC DOMAIN. [Source: SPTREMBL; Acc: Q8NFU7] CaMax: 1063b CaMax: ENSG00000167996 ENST00000301775 FERRITIN HEAVY CHAIN 11 q12.3 106a (FERRITIN H SUBUNIT). [Source: SWISSPROT; Acc: P02794] CaMax: 1070b CaMax: 1072a CaMax: 1072a CaMax: 1089d CaMax: 108a CaMax: 1090d CaMax: 1094b CaMax: 1094b CaMax: ENSMUSG00000030693 ENSMUST00000032941 7 B2 1095a ENSMUST00000014058 CaMax: ENSMUSG00000030693 ENSMUST00000032941 7 B2 1096a ENSMUST00000014058 CaMax: ENSG00000135426 ENST00000316577 12 q13.2 1098a ENST00000257883 CaMax: ENSG00000138688 ENST00000264501 4 q27 109a ENST00000306802 CaMax: ENSG00000119396 ENST00000238339 RAS-RELATED PROTEIN 9 q33.2 1105a RAB-14. [Source: SWISSPROT; Acc: P35287] CaMax: ENSG00000155755 ENST00000286196 2 q33.1 1106a CaMax: ENSG00000133121 ENST00000255486 STAR-RELATED LIPID 13 q13.1 1108a TRANSFER PROTEIN 13 (STARD13) (START DOMAIN-CONTAINING PROTEIN 13) (46H23.2). [Source: SWISSPROT; Acc: Q9Y3M8] CaMax: 1110b CaMax: 1110b CaMax: ENSG00000080546 ENST00000302071 SESTRIN 1 (P53- 6 q21 1111b ENST00000237504 REGULATED PROTEIN PA26). [Source: SWISSPROT; Acc: Q9Y6P5] CaMax: ENSG00000113391 ENST00000265139 5 q15 1112a CaMax: 111a CaMax: ENSG00000113384 ENST00000265070 GOLGI PHOSPHOPROTEIN 5 p13.3 1120a 3; GOLGI PROTEIN; GOLGI PERIPHERAL MEMBRANE PROTEIN 1, 34 KDA; GOLGI- ASSOCIATED PROTEIN; COAT-PROTEIN. [Source: RefSeq; Acc: NM_022130] CaMax: ENSG00000185511 ENST00000332847 2 p16.3 1121a CaMax: 1131b CaMax: 1132a CaMax: ENSG00000081189 ENST00000325423 MYOCYTE-SPECIFIC 5 q14.3 1134a ENHANCER FACTOR 2C. [Source: SWISSPROT; Acc: Q06413] CaMax: ENSG00000128573 ENST00000324462 FORKHEAD BOX PROTEIN 7 q31.1 1135a ENST00000265436 P2 (CAG REPEAT PROTEIN ENST00000324544 44) (TRINUCLEOTIDE REPEAT-CONTAINING GENE 10 PROTEIN). [Source: SWISSPROT; Acc: O15409] CaMax: 1137b CaMax: 1138a CaMax: 1139a CaMax: ENSG00000106817 ENST00000311316 COLLAGEN ALPHA 1(XV) 9 q22.33 1145a CHAIN PRECURSOR. [Source: SWISSPROT; Acc: P39059] CaMax: 1145a CaMax: 1146a CaMax: 1159b CaMax: ENSG00000169045 ENST00000326748 HETEROGENEOUS 5 q35.3 104a ENST00000329433 NUCLEAR RIBONUCLEOPROTEIN H (HNRNP H). [Source: SWISSPROT; Acc: P31943] CaMax: ENSG00000140416 ENST00000267996 TROPOMYOSIN 1 ALPHA 15 q22.2 1169b ENST00000334895 CHAIN (ALPHA- ENST00000288398 TROPOMYOSIN). ENST00000317516 [Source: SWISSPROT; Acc: P09493] CaMax: ENSG00000100839 ENST00000262237 DYNEIN HEAVY CHAIN, 14 q32.32 1177c CYTOSOLIC (DYHC) (CYTOPLASMIC DYNEIN HEAVY CHAIN 1) (DHC1) (FRAGMENT). [Source: SWISSPROT; Acc: Q14204] CaMax: ENSG00000156299 ENST00000286827 T-LYMPHOMA INVASION 21 q22.11 1184a AND METASTASIS INDUCING PROTEIN 1 (TIAM1 PROTEIN). [Source: SWISSPROT; Acc: Q13009] CaMax: 1184a CaMax: ENSMUSG00000038954 ENSMUST00000043985 17 C 1190b ENSMUST00000050630 CaMax: ENSMUSG00000038954 ENSMUST00000043985 17 C 1192b ENSMUST00000050630 CaMax: 11b CaMax: 120a CaMax: 120a CaMax: 1212b CaMax: ENSG00000134215 ENST00000280840 VAV-3 PROTEIN. 1 p13.3 1213d [Source: SWISSPROT; Acc: Q9UKW4] CaMax: 1217a CaMax: 1220b CaMax: 1226d CaMax: 1226d CaMax: 123c CaMax: 123c CaMax: ENSG00000065183 ENST00000183319 WD-REPEAT PROTEIN 3. 1 p12 1243a ENST00000309112 [Source: SWISSPROT; Acc: Q9UNX4] CaMax: 1245b CaMax: ENSG00000109775 ENST00000264689 4 q35.1 1246a CaMax: 1248b CaMax: ENSG00000109775 ENST00000264689 4 q35.1 1253a CaMax: 1257b CaMax: 1257b CaMax: 1260c CaMax: ENSMUSG00000045004 ENSMUST00000051907 4 D3 1263b CaMax: ENSG00000175198 ENST00000310787 PROPIONYL-COA 13 q32.3 1267a CARBOXYLASE ALPHA CHAIN, MITOCHONDRIAL PRECURSOR (EC 6.4.1.3) (PCCASE ALPHA SUBUNIT) (PROPANOYL- COA: CARBON DIOXIDE LIGASE ALPHA SUBUNIT). [Source: SWISSPROT; Acc: P05165] CaMax: ENSG00000175198 ENST00000310787 PROPIONYL-COA 13 q32.3 1267a CARBOXYLASE ALPHA CHAIN, MITOCHONDRIAL PRECURSOR (EC 6.4.1.3) (PCCASE ALPHA SUBUNIT) (PROPANOYL- COA: CARBON DIOXIDE LIGASE ALPHA SUBUNIT). [Source: SWISSPROT; Acc: P05165] CaMax: ENSG00000144331 ENST00000272761 2 q31.2 1270a CaMax: ENSG00000113615 ENST00000265341 PROTEIN TRANSPORT 5 q31.1 1272a ENST00000322887 PROTEIN SEC24A (SEC24- RELATED PROTEIN A) (FRAGMENT). [Source: SWISSPROT; Acc: O95486] CaMax: 1273b CaMax: 1276a CaMax: 127b CaMax: 127b CaMax: 1282b CaMax: 1284b CaMax: ENSG00000164190 ENST00000296607 IDN3 PROTEIN ISOFORM A. 5 p13.2 1287c ENST00000282516 [Source: RefSeq; Acc: NM_133433] CaMax: ENSG00000164190 ENST00000296607 IDN3 PROTEIN ISOFORM A. 5 p13.2 1288a ENST00000282516 [Source: RefSeq; Acc: NM_133433] CaMax: ENSMUSG00000023944 ENSMUST00000024739 HEAT SHOCK PROTEIN HSP 17 C 128a 90-BETA (HSP 84) (TUMOR SPECIFIC TRANSPLANTATION 84 KDA ANTIGEN) (TSTA). [Source: SWISSPROT; Acc: P11499] CaMax: ENSG00000079246 ENST00000328063 ATP-DEPENDENT DNA 2 q35 1292c HELICASE II, 80 KDA SUBUNIT (LUPUS KU AUTOANTIGEN PROTEIN P86) (KU86) (KU80) (86 KDA SUBUNIT OF KU ANTIGEN) (THYROID-LUPUS AUTOANTIGEN) (TLAA) (CTC BOX BINDING FACTOR 85 KDA SUBUNIT) (CTCBF) (CTC85) (NUCLEAR FACTOR IV) (DNA-REPAIR PROTEIN XRCC5). [Source: SWISSPROT; Acc: P13010] CaMax: ENSG00000136628 ENST00000259146 BIFUNCTIONAL 1 q41 1294b ENST00000335149 AMINOACYL-TRNA SYNTHETASE [INCLUDES: GLUTAMYL-TRNA SYNTHETASE (EC 6.1.1.17) (GLUTAMATE--TRNA LIGASE); PROLYL-TRNA SYNTHETASE (EC 6.1.1.15) (PROLINE--TRNA LIGASE)]. [Source: SWISSPROT; Acc: P07814] CaMax: ENSG00000163625 ENST00000295888 WD REPEAT AND FYVE 4 q21.23 1299c ENST00000322366 DOMAIN CONTAINING 3 ISOFORM 1. [Source: RefSeq; Acc: NM_014991] CaMax: 129b CaMax: 129b CaMax: 12a CaMax: ENSMUSG00000049076 ENSMUST00000058033 16 B2 1301a CaMax: ENSG00000168952 ENST00000323944 AMISYN; SYNTAXIN 14 q12 1304a BINDING PROTEIN 6. [Source: RefSeq; Acc: NM_014178] CaMax: 1308c CaMax: 1308c CaMax: 130b CaMax: 1316b CaMax: 1318a CaMax: 1320 CaMax: ENSRNOG00000003359 UDP-N- 21 q31 1322c ACETYLGLUCOSAMINE-- PEPTIDE N- ACETYLGLUCOSAMINYLTRANSFERASE 110 KDA SUBUNIT (EC 2.4.1.—) (O- GLCNAC TRANSFERASE P110 SUBUNIT). [Source: SWISSPROT; Acc: P56558] CaMax: 1323br CaMax: 1323br CaMax: 1324a CaMax: 1324a CaMax: 1335b CaMax: 1335b CaMax: ENSG00000166923 ENST00000300177 CYSTEINE KNOT 15 q13.3 1341a ENST00000322805 SUPERFAMILY 1, BMP ANTAGONIST 1; GREMLIN. [Source: RefSeq; Acc: NM_013372] CaMax: 1352b CaMax: ENSG00000171567 ENST00000304782 TIGGER TRANSPOSABLE 2 q37.1 1354a ELEMENT DERIVED 1; JERKY (MOUSE) HOMOLOG-LIKE. [Source: RefSeq; Acc: NM_145702] CaMax: 1355a CaMax: 1355a CaMax: ENSG00000033170 ENST00000315759 ALPHA-(1,6)- 14 q23.3 1361a ENST00000261677 FUCOSYLTRANSFERASE (EC 2.4.1.68) (GLYCOPROTEIN 6-ALPHA- L- FUCOSYLTRANSFERASE) (GDP-FUCOSE-- GLYCOPROTEIN FUCOSYLTRANSFERASE) (GDP-L-FUC: N-ACETYL- BETA-D-GLUCOSAMINIDE ALPHA1,6- FUCOSYLTRANSFERASE) (ALPHA1-6FUCT) (FUCOSYLTRANSFERASE 8). [Source: SWISSPROT; Acc: Q9BYC5] CaMax: 1364d CaMax: 1364d CaMax: ENSG00000064205 ENST00000190983 CONNECTIVE TISSUE 20 q13.12 1366a GROWTH FACTOR-LIKE PROTEIN PRECURSOR (CTGF-L) (WNT1 INDUCIBLE SIGNALING PATHWAY PROTEIN 2) (WISP-2) (CONNECTIVE TISSUE GROWTH FACTOR- RELATED PROTEIN 58). [Source: SWISSPROT; Acc: O76076] CaMax: ENSMUSG00000030871 ENSMUST00000033159 7 F3 1368a CaMax: ENSG00000119326 ENST00000325551 CATENIN (CADHERIN- 9 q31.3 1371a ENST00000325580 ASSOCIATED PROTEIN), ALPHA-LIKE 1; ALPHA- CATULIN. [Source: RefSeq; Acc: NM_003798] CaMax: ENSG00000083771 ENST00000218546 M-PHASE 13 q12.11 137b PHOSPHOPROTEIN 8 (FRAGMENT). [Source: SWISSPROT; Acc: Q99549] CaMax: 1381a CaMax: 1381a CaMax: ENSG00000067208 ENST00000263785 ECOTROPIC VIRAL 1 p22.1 1383a INTEGRATION SITE 5; NEUROBLASTOMA STAGE 4S GENE. [Source: RefSeq; Acc: NM_005665] CaMax: ENSG00000099194 ENST00000266053 ACYL-COA DESATURASE 10 q24.31 1384a (EC 1.14.19.1) (STEAROYL- COA DESATURASE) (FATTY ACID DESATURASE) (DELTA(9)- DESATURASE). [Source: SWISSPROT; Acc: O00767] CaMax: 1391a CaMax: 1394b CaMax: ENSG00000111912 ENST00000229634 NUCLEAR RECEPTOR 6 q22.32 1397b ENST00000318575 COACTIVATOR 7; ESTROGEN RECEPTOR ASSOCIATED PROTEIN 140 KDA. [Source: RefSeq; Acc: NM_181782] CaMax: 1399a CaMax: 13a CaMax: 1400a CaMax: ENSG00000109756 ENST00000264431 PDZ DOMAIN CONTAINING 4 q32.1 1401c GUANINE NUCLEOTIDE EXCHANGE FACTOR (GEF) 1; RA(RAS/RAP1A- ASSOCIATING)-GEF; PDZ DOMAIN CONTAINING GUANINE NUCLEOTIDE EXCHANGE FACTOR(GEF)1; RA(RAS/RAP1A- ASSOCIATING)-GEF; PDZ DOMAIN CONTAINING GUANINE NUCLEOTIDE EXCHANGE FACTOR(GEF)1. [Source: RefSeq; Acc: NM_014247] CaMax: 1403a CaMax: 1406a CaMax: ENSG00000166170 ENST00000299204 BAG-FAMILY MOLECULAR 14 q32.32 1409b CHAPERONE REGULATOR- 5 (BAG-5). [Source: SWISSPROT; Acc: Q9UL15] CaMax: ENSG00000058272 ENST00000261207 PROTEIN PHOSPHATASE 1, 12 q21.2 1411a ENST00000312727 REGULATORY (INHIBITOR) SUBUNIT 12A; MYOSIN PHOSPHATASE, TARGET SUBUNIT 1. [Source: RefSeq; Acc: NM_002480] CaMax: ENSMUSG00000034794 ENSMUST00000054209 4 C7 1415b ENSMUST00000046558 CaMax: 1416a CaMax: 1419a CaMax: 141c CaMax: 141c CaMax: 142.1c CaMax: 142.1c CaMax: ENSG00000128845 ENST00000267809 CELL CYCLE 15 q21.3 1420c ENST00000310958 PROGRESSION 8 PROTEIN. [Source: RefSeq; Acc: NM_020739] CaMax: ENSG00000172175 ENST00000313958 MUCOSA ASSOCIATED 18 q21.31 1421a ENST00000303708 LYMPHOID TISSUE LYMPHOMA TRANSLOCATION PROTEIN 1 (EC 3.4.22.—) (MALT- LYMPHOMA ASSOCIATED TRANSLOCATION) (PARACASPASE). [Source: SWISSPROT; Acc: Q9UDY8] CaMax: 1423b CaMax: ENSG00000152583 ENST00000282470 SPARC-LIKE PROTEIN 1 4 q22.1 143.2c PRECURSOR (HIGH ENDOTHELIAL VENULE PROTEIN) (HEVIN) (MAST 9). [Source: SWISSPROT; Acc: Q14515] CaMax: ENSG00000152583 ENST00000282470 SPARC-LIKE PROTEIN 1 4 q22.1 143.2c PRECURSOR (HIGH ENDOTHELIAL VENULE PROTEIN) (HEVIN) (MAST 9). [Source: SWISSPROT; Acc: Q14515] CaMax: 1431a CaMax: 144.2a CaMax: 144.2a CaMax: ENSG00000154430 ENST00000284618 TESTICAN-3 PRECURSOR. 4 q32.3 1448a [Source: SWISSPROT; Acc: Q9BQ16] CaMax: ENSG00000170631 ENST00000276816 ZINC FINGER PROTEIN 8 q24.3 1449a ENST00000317284 CLONE 647. ENST00000332620 [Source: SWISSPROT; Acc: P15622] ENST00000317099 ENST00000333589 ENST00000276823 ENST00000332158 ENST00000292579 ENST00000331465 CaMax: ENSG00000170891 ENST00000307746 CYTOKINE-LIKE PROTEIN 4 p16.2 1450a C17 PRECURSOR. [Source: SWISSPROT; Acc: Q9NRR1] CaMax: 1452a CaMax: 1457b CaMax: ENSG00000113387 ENST00000265073 ACTIVATED RNA 5 p13.3 1459c POLYMERASE II TRANSCRIPTIONAL COACTIVATOR P15 (PC4) (P14). [Source: SWISSPROT; Acc: P53999] CaMax: 1459c CaMax: ENSG00000147403 ENST00000276371 60S RIBOSOMAL PROTEIN 24 q28 145b L10 (QM PROTEIN) (TUMOR SUPPRESSOR QM) (LAMININ RECEPTOR HOMOLOG). [Source: SWISSPROT; Acc: P27635] CaMax: 1460a CaMax: 1460a CaMax: 1461a CaMax: 1461a CaMax: 1466b CaMax: 1466b CaMax: ENSMUSG00000046599 ENSMUST00000060592 UPREGULATED DURING 20 A2 1469a SKELETAL MUSCLE GROWTH 5. [Source: RefSeq; Acc: NM_023211] CaMax: ENSG00000112365 ENST00000230122 6 q21 146b CaMax: ENSMUSG00000046599 ENSMUST00000060592 UPREGULATED DURING 20 A2 1469a SKELETAL MUSCLE GROWTH 5. [Source: RefSeq; Acc: NM_023211] CaMax: 1472a CaMax: 1475a CaMax: ENSG00000172201 ENST00000326913 DNA-BINDING PROTEIN 6 p22.3 1476a INHIBITOR ID-4. [Source: SWISSPROT; Acc: P47928] CaMax: ENSG00000159388 ENST00000290551 BTG2 PROTEIN (NGF- 1 q32.1 1477a INDUCIBLE ANTI- PROLIFERATIVE PROTEIN PC3). [Source: SWISSPROT; Acc: P78543] CaMax: 147b CaMax: ENSG00000105997 ENST00000317201 HOMEOBOX PROTEIN 7 p15.2 1481c HOX-A3 (HOX-1E). [Source: SWISSPROT; Acc: O43365] CaMax: ENSG00000115998 ENST00000264434 2 p13.3 1482a CaMax: 1484b CaMax: ENSG00000122566 ENST00000265398 HETEROGENEOUS 7 p15.2 1488b ENST00000312091 NUCLEAR RIBONUCLEOPROTEINS A2/B1 (HNRNP A2/HNRNP B1). [Source: SWISSPROT; Acc: P22626] CaMax: 148a CaMax: 1497c CaMax: 1497c CaMax: 1500b CaMax: 1504d CaMax: 1506d CaMax: 1506d CaMax: ENSG00000106853 ENST00000333580 NADP-DEPENDENT 9 q31.3 150a ENST00000309195 LEUKOTRIENE B4 12- HYDROXYDEHYDROGENASE (EC 1.1.1.—). [Source: SWISSPROT; Acc: Q14914] CaMax: ENSG00000115998 ENST00000264434 2 p13.3 1516a CaMax: 1519a CaMax: 1519a CaMax: 151b CaMax: 1520a CaMax: 1520a CaMax: ENSG00000165421 ENST00000333218 PROTEIN PHOSPHATASE 11 q13.4 1521b ENST00000327431 METHYLESTERASE-1. ENST00000328257 [Source: RefSeq; Acc: NM_016147] CaMax: 1522b CaMax: 1531c CaMax: 1532a CaMax: 1532a CaMax: ENSG00000133637 ENST00000309041 12 q21.32 1534b ENST00000322687 ENST00000256013 CaMax: 1534b CaMax: 1535a CaMax: 1541a CaMax: ENSG00000151012 ENST00000280612 CYSTINE/GLUTAMATE 4 q28.3 1546b TRANSPORTER (AMINO ACID TRANSPORT SYSTEM XC-) (XCT) (CALCIUM CHANNEL BLOCKER RESISTANCE PROTEIN CCBR1). [Source: SWISSPROT; Acc: Q9UPY5] CaMax: 1548c CaMax: 1549a CaMax: ENSG00000179454 ENST00000324772 BTB (POZ) DOMAIN 14 q21.2 1551a CONTAINING 5. [Source: RefSeq; Acc: NM_017658] CaMax: 1554c CaMax: ENSG00000178074 ENST00000319974 2 q33.1 1573a CaMax: 1574b CaMax: 1574b CaMax: ENSG00000144785 ENST00000273308 TRANSMEMBRANE 12 q13.3 1577a PROTEIN 4. [Source: RefSeq; Acc: NM_014255] CaMax: 1578a CaMax: 157b CaMax: 157b CaMax: 1591a CaMax: 1591a CaMax: 1594a CaMax: 1596b CaMax: 1596b CaMax: 1598a CaMax: 159a CaMax: 159a CaMax: ENSG00000174132 ENST00000312637 5 q21.1 15b CaMax: ENSG00000113838 ENST00000265025 3 q27.3 1602a CaMax: 1604a CaMax: ENSG00000183456 ENST00000330170 2 q33.1 1626c CaMax: 1628d CaMax: 1629a CaMax: 1629a CaMax: 1630b CaMax: 1630b CaMax: ENSG00000083290 ENST00000261504 UNC-51-LIKE KINASE 2. 17 p11.2 1631d [Source: RefSeq; Acc: NM_014683] CaMax: ENSG00000083290 ENST00000261504 UNC-51-LIKE KINASE 2. 17 p11.2 1635a [Source: RefSeq; Acc: NM_014683] CaMax: ENSG00000083290 ENST00000261504 UNC-51-LIKE KINASE 2. 17 p11.2 1635a [Source: RefSeq; Acc: NM_014683] CaMax: 1639a CaMax: 1639a CaMax: ENSG00000006015 ENST00000326666 19 p13.11 163a ENST00000326636 CaMax: ENSG00000120254 ENST00000265365 6 q25.1 1646a CaMax: ENSMUSG00000033207 ENSMUST00000036069 19 C1 1648a CaMax: ENSG00000163734 ENST00000296026 MACROPHAGE 4 q13.3 164c INFLAMMATORY PROTEIN-2-BETA PRECURSOR (MIP2-BETA) (CXCL3) (GROWTH REGULATED PROTEIN GAMMA) (GRO-GAMMA). [Source: SWISSPROT; Acc: P19876] CaMax: 1659a CaMax: 1659a CaMax: ENSG00000162384 ENST00000294360 1 p32.3 166a CaMax: 1671b CaMax: 1671b CaMax: 1675a CaMax: 1676a CaMax: 1676a CaMax: 1678a CaMax: 1682a CaMax: 168c CaMax: ENSRNOG00000017817 CYTOCHROME C OXIDASE 19 q12 1690a SUBUNIT IV ISOFORM 1, MITOCHONDRIAL PRECURSOR (EC 1.9.3.1) (COX IV-1) (CYTOCHROME C OXIDASE POLYPEPTIDE IV). [Source: SWISSPROT; Acc: P10888] CaMax: ENSG00000081177 ENST00000193422 14 q24.1 1691b CaMax: ENSRNOG00000017817 CYTOCHROME C OXIDASE 19 q12 1692a SUBUNIT IV ISOFORM 1, MITOCHONDRIAL PRECURSOR (EC 1.9.3.1) (COX IV-1) (CYTOCHROME C OXIDASE POLYPEPTIDE IV). [Source: SWISSPROT; Acc: P10888] CaMax: ENSG00000066468 ENST00000263455 FIBROBLAST GROWTH 10 q26.13 1693b ENST00000310977 FACTOR RECEPTOR 2 ENST00000263451 PRECURSOR (EC 2.7.1.112) ENST00000263454 (FGFR-2) (KERATINOCYTE ENST00000328075 GROWTH FACTOR ENST00000310973 RECEPTOR 2). ENST00000263453 [Source: SWISSPROT; Acc: P21802] ENST00000332961 CaMax: 1696a CaMax: 1696a CaMax: 16b CaMax: ENSG00000132357 ENST00000254691 CASPASE RECRUITMENT 5 p13.1 1705a DOMAIN PROTEIN 6. [Source: SWISSPROT; Acc: Q9BX69] CaMax: 1709a CaMax: ENSG00000033178 ENST00000322244 4 q13.2 1714a CaMax: 1715a CaMax: ENSG00000179010 ENST00000320912 T-CELL ACTIVATION 4 p16.1 1717a PROTEIN. [Source: RefSeq; Acc: NM_033296] CaMax: ENSG00000021355 ENST00000229479 LEUKOCYTE ELASTASE 6 p25.2 1721a INHIBITOR (LEI) (MONOCYTE/NEUTROPHIL ELASTASE INHIBITOR) (M/NEI) (EI). [Source: SWISSPROT; Acc: P30740] CaMax: ENSG00000144674 ENST00000273176 GOLGI AUTOANTIGEN, 3 p22.3 1722a GOLGIN SUBFAMILY A MEMBER 4 (TRANS-GOLGI P230) (256 KDA GOLGIN) (GOLGIN-245) (72.1 PROTEIN). [Source: SWISSPROT; Acc: Q13439] CaMax: ENSG00000143147 ENST00000271357 G-PROTEIN COUPLED 1 q24.2 1724a RECEPTOR. [Source: RefSeq; Acc: NM_153832] CaMax: 1725a CaMax: 1726a CaMax: 1726a CaMax: ENSG00000131355 ENST00000253673 EGF-LIKE MODULE- 19 p13.12 1727a CONTAINING MUCIN-LIKE RECEPTOR 3 ISOFORM A. [Source: RefSeq; Acc: NM_032571] CaMax: 1730a CaMax: 1738b CaMax: 1741a CaMax: ENSG00000109883 ENST00000227288 LEUCINE-RICH REPEAT- 11 p14.1 1744a CONTAINING G PROTEIN- COUPLED RECEPTOR 4 PRECURSOR (G PROTEIN- COUPLED RECEPTOR 48). [Source: SWISSPROT; Acc: Q9BXB1] CaMax: 1744a CaMax: ENSG00000139688 ENST00000267164 TRANSCRIPTION 13 q14.12 174a INITIATION FACTOR IIF, BETA SUBUNIT (TFIIF- BETA) (TRANSCRIPTION INITIATION FACTOR RAP30). [Source: SWISSPROT; Acc: P13984] CaMax: 174a CaMax: 1750a CaMax: 1751a CaMax: 1755a CaMax: 1755a CaMax: ENSG00000104852 ENST00000221448 U1 SMALL NUCLEAR 19 q13.33 1758a RIBONUCLEOPROTEIN 70 KDA (U1 SNRNP 70 KDA) (SNRNP70) (U1-70K). [Source: SWISSPROT; Acc: P08621] CaMax: ENSG00000179454 ENST00000324772 BTB (POZ) DOMAIN 14 q21.2 1759b CONTAINING 5. [Source: RefSeq; Acc: NM_017658] CaMax: 1760c CaMax: 1760c CaMax: 1772a CaMax: ENSG00000179562 ENST00000321407 GOLGI COILED COIL 7 q32.1 1775a PROTEIN 1. [Source: SWISSPROT; Acc: Q96CN9] CaMax: ENSG00000179562 ENST00000321407 GOLGI COILED COIL 7 q32.1 1775a PROTEIN 1. [Source: SWISSPROT; Acc: Q96CN9] CaMax: 1778c CaMax: ENSG00000184880 ENST00000332933 OK/SW-CL.87. 11 q23.3 1782b [Source: SPTREMBL; Acc: Q8NI68] CaMax: ENSG00000135457 ENST00000257915 TRANSCRIPTION FACTOR 12 q13.12 178a ENST00000307660 CP2; TRANSCRIPTION FACTOR CP2, ALPHA GLOBIN. [Source: RefSeq; Acc: NM_005653] CaMax: 1794a CaMax: 1794a CaMax: 17a CaMax: 1800a CaMax: ENSG00000166855 ENST00000300107 ATP-DEPENDENT CLP 15 q22.31 1801b PROTEASE ATP-BINDING SUBUNIT CLPX-LIKE, MITOCHONDRIAL PRECURSOR. [Source: SWISSPROT; Acc: O76031] CaMax: ENSG00000171567 ENST00000304782 TIGGER TRANSPOSABLE 2 q37.1 180a ELEMENT DERIVED 1; JERKY (MOUSE) HOMOLOG-LIKE. [Source: RefSeq; Acc: NM_145702] CaMax: ENSG00000102901 ENST00000219172 16 q22.1 1810a CaMax: 1811b CaMax: ENSG00000105492 ENST00000270604 SIALIC ACID BINDING IG- 19 q13.41 1812b LIKE LECTIN 6 PRECURSOR (SIGLEC-6) (OBESITY-BINDING PROTEIN 1) (OB-BP1) (CD33 ANTIGEN-LIKE 1). [Source: SWISSPROT; Acc: O43699] CaMax: ENSG00000145730 ENST00000304400 PEPTIDYL-GLYCINE 5 q21.1 1814c ENST00000304406 ALPHA-AMIDATING ENST00000282992 MONOOXYGENASE ENST00000325306 PRECURSOR (EC 1.14.17.3) ENST00000274392 (PAM). [Source: SWISSPROT; Acc: P19021] CaMax: 1814c CaMax: 1818a CaMax: ENSMUSG00000021613 ENSMUST00000053227 PROTEOGLYCAN LINK 13 C3 1828b ENSMUST00000022108 PROTEIN PRECURSOR (CARTILAGE LINK PROTEIN) (LP). [Source: SWISSPROT; Acc: Q9QUP5] CaMax: 1834b CaMax: 1849d CaMax: 1852a CaMax: ENSRNOG00000013516 SPLICEOSOMAL PROTEIN 9 q31 1853a SAP155 (FRAGMENT). [Source: SPTREMBL; Acc: Q9ET34] CaMax: ENSRNOG00000015205 CYTOCHROME B5. 18 q12.3 1857c [Source: SWISSPROT; Acc: P00173] CaMax: ENSG00000055609 ENST00000312661 MYELOID/LYMPHOID OR 7 q36.1 1859a ENST00000262189 MIXED-LINEAGE LEUKEMIA 3; ALR-LIKE PROTEIN. [Source: RefSeq; Acc: NM_021230] CaMax: 1863c CaMax: 1863c CaMax: ENSMUSG00000033732 ENSMUST00000042012 8 D3 1864b ENSMUST00000054613 CaMax: ENSG00000173210 ENST00000309868 5 q33.1 186a ENST00000326685 CaMax: 1874b CaMax: 1874b CaMax: 1879a CaMax: 1879a CaMax: 1881b CaMax: ENSG00000151806 ENST00000281543 4 p13 1894a CaMax: 18a CaMax: 1912a CaMax: 1912a CaMax: 1913a CaMax: 1913a CaMax: ENSG00000146414 ENST00000275233 SNF2 HISTONE LINKER 6 q24.3 1917f ENST00000334592 PHD RING HELICASE. [Source: RefSeq; Acc: NM_173082] CaMax: ENSG00000057019 ENST00000326857 ENDOTHELIAL AND 3 q12.1 1919a ENST00000326840 SMOOTH MUSCLE CELL- DERIVED NEUROPILIN- LIKE PROTEIN; COAGULATION FACTOR V/VIII-HOMOLOGY DOMAINS PROTEIN 1. [Source: RefSeq; Acc: NM_080927] CaMax: ENSMUSG00000022649 ENSMUST00000052314 16 B5 1920a ENSMUST00000023327 CaMax: 1928a CaMax: ENSG00000142207 ENST00000270201 21 q22.11 1929c CaMax: ENSG00000117868 ENST00000251527 7 q36.3 1930a CaMax: ENSG00000116957 ENST00000264180 BETA-TUBULIN 1 q42.3 1940e COFACTOR E. [Source: RefSeq; Acc: NM_003193] CaMax: ENSG00000070214 ENST00000185520 CDW92 ANTIGEN; 9 q31.1 1941e CHOLINE TRANSPORTER- LIKE PROTEIN. [Source: RefSeq; Acc: NM_080546] CaMax: ENSG00000154553 ENST00000284770 ALPHA-ACTININ-2- 4 q35.1 1943a ENST00000284771 ASSOCIATED LIM ENST00000284767 PROTEIN; ENIGMA HOMOLOG. [Source: RefSeq; Acc: NM_014476] CaMax: 1944a CaMax: 1944a CaMax: 1945a CaMax: 1945a CaMax: 1948b CaMax: 1948b CaMax: 1949a CaMax: 1949a CaMax: ENSG00000134215 ENST00000280840 VAV-3 PROTEIN. 1 p13.3 1950a [Source: SWISSPROT; Acc: Q9UKW4] CaMax: ENSG00000138386 ENST00000321041 NGFI-A BINDING PROTEIN 2 q32.2 1953a 1 (EGR-1 BINDING PROTEIN 1) (TRANSCRIPTIONAL REGULATORY PROTEIN P54). [Source: SWISSPROT; Acc: Q13506] CaMax: 1954e CaMax: ENSG00000157077 ENST00000287722 MOTHERS AGAINST 1 p32.3 1961e ENST00000287727 DECAPENTAPLEGIC HOMOLOG INTERACTING PROTEIN (MADH- INTERACTING PROTEIN) (SMAD ANCHOR FOR RECEPTOR ACTIVATION) (RECEPTOR ACTIVATION ANCHOR) (HSARA) (NOVEL SERINE PROTEASE) (NSP). [Source: SWISSPROT; Acc: O95405] CaMax: ENSG00000080469 ENST00000328494 ANTIGEN PEPTIDE 6 p21.32 1967a ENST00000190846 TRANSPORTER 2 (APT2) (PEPTIDE TRANSPORTER TAP2) (PEPTIDE TRANSPORTER PSF2) (PEPTIDE SUPPLY FACTOR 2) (PSF-2) (PEPTIDE TRANSPORTER INVOLVED IN ANTIGEN PROCESSING 2). [Source: SWISSPROT; Acc: Q03519] CaMax: ENSG00000138063 ENST00000260632 PELLINO PROTEIN. 2 p14 1968a [Source: RefSeq; Acc: NM_020651] CaMax: ENSG00000060718 ENST00000305302 COLLAGEN ALPHA 1 (XI) 1 p21.1 1982a ENST00000193186 CHAIN PRECURSOR. ENST00000314022 [Source: SWISSPROT; Acc: P12107] ENST00000305262 CaMax: 1989b CaMax: ENSG00000166974 ENST00000300249 MICROTUBULE- 18 q12.1 1990a ASSOCIATED PROTEIN, RP/EB FAMILY, MEMBER 2; T-CELL ACTIVATION PROTEIN, EB1 FAMILY; APC-BINDING PROTEIN EB1. [Source: RefSeq; Acc: NM_014268] CaMax: 1991d CaMax: 1a CaMax: 2002c CaMax: ENSG00000081019 ENST00000261441 1 p13.2 2003a CaMax: ENSMUSG00000027883 ENSMUST00000029482 PINS. 3 F3 2008a [Source: RefSeq; Acc: NM_029522] CaMax: ENSG00000180530 ENST00000318948 NUCLEAR FACTOR RIP140 21 q11.2 2013a (NUCLEAR RECEPTOR INTERACTING PROTEIN 1). [Source: SWISSPROT; Acc: P48552] CaMax: 2014f CaMax: ENSG00000174444 ENST00000307961 60S RIBOSOMAL PROTEIN 15 q22.31 2015e L4 (L1). [Source: SWISSPROT; Acc: P36578] CaMax: ENSG00000011566 ENST00000263881 MITOGEN-ACTIVATED 2 p22.1 2020b PROTEIN KINASE KINASE KINASE KINASE 3 (EC 2.7.1.37) (MAPK/ERK KINASE KINASE KINASE 3) (MEK KINASE KINASE 3) (MEKKK 3) (GERMINAL CENTER KINASE RELATED PROTEIN KINASE) (GLK). [Source: SWISSPROT; Acc: Q8IVH8] CaMax: 2020b CaMax: ENSG00000020577 ENST00000305831 14 q22.2 2022a ENST00000251091 ENST00000321411 CaMax: 2023b CaMax: 2023b CaMax: 2024a CaMax: ENSG00000172155 ENST00000326233 LATE ENVELOPE PROTEIN 1 q21.3 2034a 4. [Source: RefSeq; Acc: NM_178352] CaMax: ENSG00000161980 ENST00000293860 DNA-DIRECTED RNA 16 p13.3 2035d POLYMERASES III 12.5 KDA POLYPEPTIDE (EC 2.7.7.6) (RNA POLYMERASE III C11 SUBUNIT) (HSC11P) (HRPC11) (MY010 PROTEIN). [Source: SWISSPROT; Acc: Q9Y2Y1] CaMax: 204a CaMax: ENSG00000141331 ENST00000269073 POTENTIAL HELICASE 17 q24.2 2056d WITH ZINC-FINGER DOMAIN. [Source: SWISSPROT; Acc: P42694] CaMax: 2059b CaMax: 205a CaMax: ENSG00000129116 ENST00000261509 PALLADIN; CGI-151 4 q32.3 2070a ENST00000335213 PROTEIN. ENST00000333488 [Source: RefSeq; Acc: NM_016081] CaMax: 2073b CaMax: 2073b CaMax: ENSG00000124406 ENST00000264449 POTENTIAL 4 p13 2074b PHOSPHOLIPID- TRANSPORTING ATPASE IA (EC 3.6.3.1) (CHROMAFFIN GRANULE ATPASE II) (ATPASE CLASS I TYPE 8A MEMBER 1). [Source: SWISSPROT; Acc: Q9Y2Q0] CaMax: ENSG00000138709 ENST00000264584 4 q28.2 2075a ENST00000326703 ENST00000326639 CaMax: 2076c CaMax: ENSG00000122545 ENST00000322406 SEPTIN 7 (CDC10 PROTEIN 7 p14.2 2078a HOMOLOG). [Source: SWISSPROT; Acc: Q16181] CaMax: ENSG00000085449 ENST00000233055 WD REPEAT AND FYVE 2 q36.1 2083e ENST00000272881 DOMAIN CONTAINING 1 ISOFORM 1; PHOSPHOINOSITIDE- BINDING PROTEIN SR1; WD40 AND FYVE DOMAIN CONTAINING 1. [Source: RefSeq; Acc: NM_020830] CaMax: ENSG00000152487 ENST00000302150 10 p12.31 2088a CaMax: 2092c CaMax: 2095a CaMax: 2099a CaMax: 2099a CaMax: 20a CaMax: 20a CaMax: ENSG00000166147 ENST00000316623 FIBRILLIN 1 PRECURSOR. 15 q21.1 2100b [Source: SWISSPROT; Acc: P35555] CaMax: 2105a CaMax: 2108b CaMax: 2109a CaMax: ENSG00000180837 ENST00000318177 ZINC FINGER PROTEIN 345 19 q13.12 2110a (ZINC FINGER PROTEIN HZF10). [Source: SWISSPROT; Acc: Q14585] CaMax: 2113a CaMax: ENSG00000103222 ENST00000263013 MULTIDRUG RESISTANCE- 16 p13.11 211b ENST00000263018 ASSOCIATED PROTEIN 1. ENST00000263015 [Source: SWISSPROT; Acc: P33527] ENST00000263019 ENST00000263017 ENST00000263014 ENST00000263016 CaMax: 2122a CaMax: ENSG00000139370 ENST00000266771 PEPTIDE-HISTIDINE 12 q24.32 2123a TRANSPORTER 4. [Source: RefSeq; Acc: NM_145648] CaMax: ENSG00000143415 ENST00000271682 SMALL PROTEIN 1 q21.3 2129a EFFECTOR 1 OF CDC42. [Source: RefSeq; Acc: NM_020239] CaMax: 2132a CaMax: 2135d CaMax: 2136b CaMax: 2141a CaMax: 2142a CaMax: 2160a CaMax: ENSG00000138709 ENST00000264584 4 q28.2 2161c ENST00000326703 ENST00000326639 CaMax: 2165a CaMax: 2167a CaMax: 2189b CaMax: 2198b CaMax: 2201a CaMax: 2201a CaMax: 2205a CaMax: 2210a CaMax: ENSG00000117868 ENST00000251527 7 q36.3 2222b CaMax: 2223a CaMax: ENSG00000116690 ENST00000251819 PROTEOGLYCAN 4; 1 q31.1 2224a MEGAKARYOCYTE STIMULATING FACTOR; PROTEOGLYCAN 4, (MEGAKARYOCYTE STIMULATING FACTOR, ARTICULAR SUPERFICIAL ZONE PROTEIN); JACOBS CAMPTODACTYLY- ARTHROPATHY- PERICARDITIS SYNDROME; CAMPTODACTYLY, ARTHROPATHY, COXA VARA, PERICARDITIS SYNDROME. [Source: RefSeq; Acc: NM_005807] CaMax: ENSG00000151544 ENST00000281234 10 q25.3 2225b CaMax: ENSMUSG00000038760 ENSMUST00000038856 THYROTROPIN- 15 D1 2234a RELEASING HORMONE RECEPTOR (TRH-R) (THYROLIBERIN RECEPTOR). [Source: SWISSPROT; Acc: P21761] CaMax: 2235a CaMax: 2235a CaMax: ENSG00000172572 ENST00000325802 CGMP-INHIBITED 3′,5′- 12 p12.2 2238a CYCLIC PHOSPHODIESTERASE A (EC 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE A) (CGI-PDE A). [Source: SWISSPROT; Acc: Q14432] CaMax: ENSG00000172572 ENST00000325802 CGMP-INHIBITED 3′,5′- 12 p12.2 2241a CYCLIC PHOSPHODIESTERASE A (EC 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE A) (CGI-PDE A). [Source: SWISSPROT; Acc: Q14432] CaMax: ENSG00000172572 ENST00000325802 CGMP-INHIBITED 3′,5′- 12 p12.2 2238a CYCLIC PHOSPHODIESTERASE A (EC 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE A) (CGI-PDE A). [Source: SWISSPROT; Acc: Q14432] CaMax: 224a CaMax: 2251d CaMax: ENSG00000109775 ENST00000264689 4 q35.1 2252b CaMax: 2258a CaMax: 2258a CaMax: 2258a CaMax: 225a CaMax: 2264b CaMax: 2264b CaMax: 2266b CaMax: ENSG00000137801 ENST00000260356 THROMBOSPONDIN 1 15 q14 2267a PRECURSOR. [Source: SWISSPROT; Acc: P07996] CaMax: 231a CaMax: 2331c CaMax: ENSG00000119397 ENST00000238341 9 q33.2 2341b CaMax: 2351c CaMax: 2351c CaMax: ENSG00000172572 ENST00000325802 CGMP-INHIBITED 3′,5′- 12 p12.2 2241a CYCLIC PHOSPHODIESTERASE A (EC 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE A) (CGI-PDE A). [Source: SWISSPROT; Acc: Q14432] CaMax: 235a CaMax: ENSG00000137801 ENST00000260356 THROMBOSPONDIN 1 15 q14 2374a PRECURSOR. [Source: SWISSPROT; Acc: P07996] CaMax: 238a CaMax: ENSG00000119363 ENST00000238302 SPECTRIN ALPHA CHAIN, 9 q34.11 239a BRAIN (SPECTRIN, NON- ERYTHROID ALPHA CHAIN) (ALPHA-II SPECTRIN) (FODRIN ALPHA CHAIN). [Source: SWISSPROT; Acc: Q13813] CaMax: ENSG00000162419 ENST00000294409 GLUCOCORTICOID 1 p35.3 23a MODULATORY ELEMENT BINDING PROTEIN 1 (GMEB-1) (PARVOVIRUS INITIATION FACTOR P96) (PIF P96) (DNA BINDING PROTEIN P96PIF). [Source: SWISSPROT; Acc: Q9Y692] CaMax: ENSG00000154144 ENST00000284290 11 q24.2 240a CaMax: 243a CaMax: ENSG00000166800 ENST00000280706 11 p15.1 245a CaMax: ENSG00000162437 ENST00000294428 1 p31.3 248a CaMax: 24a CaMax: 258a CaMax: 261c CaMax: 261c CaMax: ENSG00000041982 ENST00000265131 TENASCIN PRECURSOR 9 q33.1 267d (TN) (HEXABRACHION) (CYTOTACTIN) (NEURONECTIN) (GMEM) (JI) (MIOTENDINOUS ANTIGEN) (GLIOMA- ASSOCIATED- EXTRACELLULAR MATRIX ANTIGEN) (GP 150-225) (TENASCIN-C) (TN-C). [Source: SWISSPROT; Acc: P24821] CaMax: ENSG00000141642 ENST00000269466 ELAC HOMOLOG 1. 18 q21.1 272d [Source: RefSeq; Acc: NM_018696] CaMax: 27a CaMax: 28s CaMax: ENSG00000141378 ENST00000311824 PROTEIN CGI-147. 17 q23.2 307b [Source: SWISSPROT; Acc: Q9Y3E5] CaMax: ENSG00000116745 ENST00000262340 RETINAL PIGMENT 1 p31.2 308c EPITHELIUM-SPECIFIC PROTEIN 65 KDA; RETINAL PIGMENT EPITHELIUM- SPECIFIC PROTEIN (65 KD); RETINITIS PIGMENTOSA 20 (AUTOSOMAL RECESSIVE). [Source: RefSeq; Acc: NM_000329] CaMax: 310h CaMax: 311c CaMax: 313a CaMax: 314a CaMax: 319b CaMax: ENSG00000090989 ENST00000317642 EXOCYST COMPLEX 4 q12 320a ENST00000333951 COMPONENT SEC3 (BM- 012). [Source: SWISSPROT; Acc: Q9NV70] CaMax: 320a CaMax: 322a CaMax: ENSG00000135913 ENST00000258399 2 q35 324a CaMax: ENSMUSG00000025724 ENSMUST00000026818 MICROSOMAL SIGNAL 7 D2 326e PEPTIDASE 18 KDA SUBUNIT (EC 3.4.—.—) (SPASE 18 KDA SUBUNIT) (SPC18) (ENDOPEPTIDASE SP18). [Source: SWISSPROT; Acc: Q9R0P6] CaMax: 327f CaMax: 327f CaMax: ENSG00000129116 ENST00000261509 PALLADIN; CGI-151 4 q32.3 328b ENST00000335213 PROTEIN. ENST00000333488 [Source: RefSeq; Acc: NM_016081] CaMax: ENSG00000173320 ENST00000308497 4 q35.1 336a CaMax: 33a CaMax: 33a CaMax: 340a CaMax: 340a CaMax: 343b CaMax: 343b CaMax: 34a CaMax: 34a CaMax: ENSG00000167996 ENST00000301775 FERRITIN HEAVY CHAIN 11 q12.3 106a (FERRITIN H SUBUNIT). [Source: SWISSPROT; Acc: P02794] CaMax: ENSG00000167996 ENST00000301775 FERRITIN HEAVY CHAIN 11 q12.3 106a (FERRITIN H SUBUNIT). [Source: SWISSPROT; Acc: P02794] CaMax: 360a CaMax: 360a CaMax: ENSG00000182944 ENST00000331029 RNA-BINDING PROTEIN 22 q12.2 364a ENST00000329871 EWS (EWS ONCOGENE) (EWING SARCOMA BREAKPOINT REGION 1 PROTEIN). [Source: SWISSPROT; Acc: Q01844] CaMax: 370a CaMax: ENSG00000136938 ENST00000277182 ACIDIC LEUCINE-RICH 9 q22.33 374a NUCLEAR PHOSPHOPROTEIN 32 FAMILY MEMBER B (PHAPI2 PROTEIN) (SILVER-STAINABLE PROTEIN SSP29) (ACIDIC PROTEIN RICH IN LEUCINES). [Source: SWISSPROT; Acc: Q92688] CaMax: 375d CaMax: 379a CaMax: ENSG00000145216 ENST00000306932 FIP1-LIKE 1; REARRANGED 4 q12 38a ENST00000273816 IN HYPEREOSINOPHILIA. [Source: RefSeq; Acc: NM_030917] CaMax: 391a CaMax: 392a CaMax: 392a CaMax: 395a CaMax: 395a CaMax: 397b CaMax: ENSRNOG00000006864 8 q24 3c CaMax: 406a-r CaMax: 406a-r CaMax: 408a CaMax: 409a CaMax: ENSG00000134001 ENST00000256383 EUKARYOTIC 14 q23.3 415b TRANSLATION INITIATION FACTOR 2 SUBUNIT 1 (EUKARYOTIC TRANSLATION INITIATION FACTOR 2 ALPHA SUBUNIT) (EIF-2-ALPHA) (EIF-2ALPHA) (EIF-2A). [Source: SWISSPROT; Acc: P05198] CaMax: 421a CaMax: ENSG00000174132 ENST00000312637 5 q21.1 43a CaMax: 446f CaMax: 44c CaMax: 44c CaMax: 45.1b CaMax: 45.1b CaMax: 450a CaMax: 450a CaMax: 452a CaMax: 455c CaMax: 455c CaMax: 457c CaMax: ENSG00000102908 ENST00000317142 NUCLEAR FACTOR OF 16 q22.1 459a ACTIVATED T CELLS 5 (T CELL TRANSCRIPTION FACTOR NFAT5) (NF-AT5) (TONICITY-RESPONSIVE ENHANCER-BINDING PROTEIN) (TONE-BINDING PROTEIN) (TONEBP). [Source: SWISSPROT; Acc: O94916] CaMax: 461a CaMax: 461a CaMax: ENSG00000035687 ENST00000263828 ADENYLOSUCCINATE 1 q44 464b SYNTHETASE (EC 6.3.4.4) (IMP--ASPARTATE LIGASE) (ADSS) (AMPSASE). [Source: SWISSPROT; Acc: P30520] CaMax: ENSG00000064309 ENST00000263577 SURFACE GLYCOPROTEIN, 11 q24.2 465b IG SUPERFAMILY MEMBER. [Source: RefSeq; Acc: NM_016952] CaMax: 46a CaMax: 472a CaMax: 472a CaMax: ENSG00000165169 ENST00000297871 T-COMPLEX ASSOCIATED- 24 p11.4 478a TESTIS-EXPRESSED 1-LIKE (PROTEIN 91/23). [Source: SWISSPROT; Acc: P51808] CaMax: ENSG00000165169 ENST00000297871 T-COMPLEX ASSOCIATED- 24 p11.4 479c TESTIS-EXPRESSED 1-LIKE (PROTEIN 91/23). [Source: SWISSPROT; Acc: P51808] CaMax: 482a CaMax: ENSG00000116584 ENST00000313695 RHO GUANINE 1 q22 487a ENST00000313667 NUCLEOTIDE EXCHANGE FACTOR 2 (GEF-H1 PROTEIN) (PROLIFERATING CELL NUCLEOLAR ANTIGEN P40). [Source: SWISSPROT; Acc: Q92974] CaMax: ENSG00000159399 ENST00000290573 HEXOKINASE, TYPE II (EC 2 p12 488a 2.7.1.1) (HK II) (MUSCLE FORM HEXOKINASE). [Source: SWISSPROT; Acc: P52789] CaMax: 48b CaMax: 48b CaMax: 490c CaMax: 490c CaMax: 494a CaMax: 494a CaMax: 498a CaMax: 50.1c CaMax: 50.1c CaMax: 501b CaMax: 504a CaMax: 505b CaMax: 507a CaMax: 516c CaMax: 517c CaMax: 51a CaMax: 51a CaMax: ENSG00000179454 ENST00000324772 BTB (POZ) DOMAIN 14 q21.2 520a CONTAINING 5. [Source: RefSeq; Acc: NM_017658] CaMax: ENSG00000081189 ENST00000325423 MYOCYTE-SPECIFIC 5 q14.3 521b ENHANCER FACTOR 2C. [Source: SWISSPROT; Acc: Q06413] CaMax: 523a CaMax: 52a CaMax: ENSG00000100567 ENST00000216455 PROTEASOME SUBUNIT 14 q23.1 530b ALPHA TYPE 3 (EC 3.4.25.1) (PROTEASOME COMPONENT C8) (MACROPAIN SUBUNIT C8) (MULTICATALYTIC ENDOPEPTIDASE COMPLEX SUBUNIT C8). [Source: SWISSPROT; Acc: P25788] CaMax: 538a CaMax: ENSG00000133059 ENST00000255422 HDCMD38P. 1 q32.1 539a ENST00000335353 [Source: SPTREMBL; Acc: Q9P1S5] CaMax: 540a CaMax: 543a CaMax: ENSG00000144785 ENST00000273308 TRANSMEMBRANE 12 q13.3 545a PROTEIN 4. [Source: RefSeq; Acc: NM_014255] CaMax: ENSG00000174560 ENST00000310012 6 q12 547c CaMax: ENSG00000174560 ENST00000310012 6 q12 548c CaMax: ENSG00000133226 ENST00000334537 SER/ARG-RELATED 1 p36.11 550a ENST00000323848 NUCLEAR MATRIX PROTEIN (PLENTY OF PROLINES 101-L; SER/ARG- RELATED NUCLEAR MATRIX PROTEIN (PLENTY OF PROLINES 101-LIKE). [Source: RefSeq; Acc: NM_005839] CaMax: 552a CaMax: ENSG00000180185 ENST00000326061 16 p13.3 553b CaMax: ENSG00000005812 ENST00000281993 F-BOX AND LEUCINE-RICH 13 q22.3 555b REPEAT PROTEIN 3A; F- BOX PROTEIN FBL3A. [Source: RefSeq; Acc: NM_012158] CaMax: 556b CaMax: 557b CaMax: 558a CaMax: 558a CaMax: 560b CaMax: 561b CaMax: 568a CaMax: 568a CaMax: 56a CaMax: 56a CaMax: ENSG00000143924 ENST00000318522 ECHINODERM 2 p21 571a MICROTUBULE- ASSOCIATED PROTEIN- LIKE 4 (EMAP-4) (RESTRICTEDLY OVEREXPRESSED PROLIFERATION- ASSOCIATED PROTEIN) (ROPP 120). [Source: SWISSPROT; Acc: Q9HC35] CaMax: 574a CaMax: ENSG00000124193 ENST00000244020 SPLICING FACTOR, 20 q13.11 579a ARGININE/SERINE-RICH 6 (PRE-MRNA SPLICING FACTOR SRP55). [Source: SWISSPROT; Acc: Q13247] CaMax: ENSG00000091409 ENST00000264107 INTEGRIN ALPHA-6 2 q31.1 57a ENST00000264106 PRECURSOR (VLA-6) (CD49F). [Source: SWISSPROT; Acc: P23229] CaMax: ENSG00000115112 ENST00000263707 LBP-9. 2 q14.2 581a [Source: RefSeq; Acc: NM_014553] CaMax: ENSMUSG00000026193 ENSMUST00000055226 1 C3 583e ENSMUST00000059577 ENSMUST00000027385 CaMax: 58a CaMax: ENSG00000171634 ENST00000306378 FETAL ALZHEIMER 17 q24.2 597c ENST00000335221 ANTIGEN (FETAL ALZ-50- ENST00000321866 REACTIVE CLONE 1). ENST00000321892 [Source: SWISSPROT; Acc: Q12830] CaMax: 59a CaMax: 59a CaMax: 609a CaMax: 611a CaMax: 622a CaMax: 622a CaMax: ENSG00000140575 ENST00000268182 RAS GTPASE-ACTIVATING- 15 q26.1 623a LIKE PROTEIN IQGAP1 (P195). [Source: SWISSPROT; Acc: P46940] CaMax: 624b CaMax: 626a CaMax: 626a CaMax: ENSG00000183762 ENST00000327813 KREMEN PROTEIN 1 22 q12.1 628a PRECURSOR (KRINGLE- CONTAINING PROTEIN MARKING THE EYE AND THE NOSE) (DICKKOPF RECEPTOR). [Source: SWISSPROT; Acc: Q96MU8] CaMax: ENSG00000133226 ENST00000334537 SER/ARG-RELATED 1 p36.11 635a ENST00000323848 NUCLEAR MATRIX PROTEIN (PLENTY OF PROLINES 101-L; SER/ARG- RELATED NUCLEAR MATRIX PROTEIN (PLENTY OF PROLINES 101-LIKE). [Source: RefSeq; Acc: NM_005839] CaMax: ENSG00000165169 ENST00000297871 T-COMPLEX ASSOCIATED- 24 p11.4 638b TESTIS-EXPRESSED 1-LIKE (PROTEIN 91/23). [Source: SWISSPROT; Acc: P51808] CaMax: 639a CaMax: 63a CaMax: 63a CaMax: ENSG00000144560 ENST00000273038 3 p25.3 64.2a CaMax: ENSG00000125149 ENST00000219139 UPF0183 PROTEIN. 16 q22.1 685a [Source: SWISSPROT; Acc: Q9BSU1] CaMax: 690a CaMax: 690a CaMax: ENSG00000171567 ENST00000304782 TIGGER TRANSPOSABLE 2 q37.1 692a ELEMENT DERIVED 1; JERKY (MOUSE) HOMOLOG-LIKE. [Source: RefSeq; Acc: NM_145702] CaMax: ENSRNOG00000007325 8 q23 697a CaMax: 6b CaMax: ENSMUSG00000032077 ENSMUST00000036099 9 B 701a CaMax: ENSG00000119509 ENST00000262457 INVERSIN. 9 q22.33 704b ENST00000262456 [Source: RefSeq; Acc: NM_014425] CaMax: ENSG00000119509 ENST00000262457 INVERSIN. 9 q22.33 704b ENST00000262456 [Source: RefSeq; Acc: NM_014425] CaMax: 70d CaMax: ENSG00000123500 ENST00000243222 COLLAGEN ALPHA 1(X) 6 q22.1 710a CHAIN PRECURSOR. [Source: SWISSPROT; Acc: Q03692] CaMax: 711a CaMax: 711a CaMax: 713a CaMax: 713a CaMax: 714a CaMax: 718a CaMax: 720a CaMax: ENSG00000133454 ENST00000335473 22 q12.1 725a ENST00000335460 ENST00000335471 ENST00000335359 CaMax: ENSG00000122912 ENST00000265870 GRAVE'S DISEASE 10 q21.3 726b CARRIER PROTEIN (GDC) (GRAVE'S DISEASE AUTOANTIGEN) (GDA) (MITOCHONDRIAL SOLUTE CARRIER PROTEIN HOMOLOG). [Source: SWISSPROT; Acc: P16260] CaMax: 72a CaMax: 72a CaMax: 731a CaMax: 731a CaMax: ENSG00000130066 ENST00000252349 DIAMINE 24 p22.11 736a ACETYLTRANSFERASE (EC 2.3.1.57) (SPERMIDINE/SPERMINE N(1)- ACETYLTRANSFERASE) (SSAT) (PUTRESCINE ACETYLTRANSFERASE). [Source: SWISSPROT; Acc: P21673] CaMax: ENSG00000166938 ENST00000319194 15 q22.31 739a ENST00000319212 CaMax: ENSG00000112473 ENST00000230235 HISTIDINE-RICH 6 p21.32 73b ENST00000325843 MEMBRANE PROTEIN KE4. [Source: SWISSPROT; Acc: Q92504] CaMax: 745a CaMax: ENSG00000164190 ENST00000296607 IDN3 PROTEIN ISOFORM A. 5 p13.2 747a ENST00000282516 [Source: RefSeq; Acc: NM_133433] CaMax: 749a CaMax: 74c CaMax: ENSMUSG00000039203 ENSMUST00000036300 4 C1 753b CaMax: 759b CaMax: 759b CaMax: 764b CaMax: 764b CaMax: ENSG00000102763 ENST00000251030 13 q14.11 765a ENST00000281496 CaMax: 768a CaMax: 76b CaMax: ENSG00000171867 ENST00000305832 MAJOR PRION PROTEIN 20 p13 785b PRECURSOR (PRP) (PRP27-30) (PRP33-35C) (ASCR) (CD230 ANTIGEN). [Source: SWISSPROT; Acc: P04156] CaMax: 788a CaMax: ENSG00000102471 ENST00000218652 13 q31.1 789a CaMax: ENSG00000123096 ENST00000242729 SARCOSPAN (K-RAS 12 p12.1 794a ONCOGENE-ASSOCIATED PROTEIN) (KIRSTEN-RAS- ASSOCIATED PROTEIN). [Source: SWISSPROT; Acc: Q14714] CaMax: ENSG00000106554 ENST00000262570 7 q32.3 795a CaMax: ENSG00000131388 ENST00000253706 3 p25.1 810a CaMax: 813a CaMax: 815a CaMax: 81a CaMax: 820a CaMax: 820a CaMax: 827b CaMax: 827b CaMax: 828a CaMax: 82b CaMax: 831a CaMax: 831a CaMax: ENSMUSG00000026193 ENSMUST00000055226 1 C3 832a ENSMUST00000059577 ENSMUST00000027385 CaMax: ENSG00000090581 ENST00000204679 16 p13.3 833a CaMax: 835c CaMax: ENSG00000068885 ENST00000326448 3 q25.33 839a CaMax: 841b CaMax: 841b CaMax: 847a CaMax: ENSG00000136003 ENST00000311893 NITROGEN FIXATION 12 q23.3 85.1c ENST00000228459 CLUSTER-LIKE. [Source: RefSeq; Acc: NM_014301] CaMax: ENSG00000149218 ENST00000278505 11 q21 85.2b CaMax: 850a CaMax: 851a CaMax: ENSG00000060982 ENST00000261192 BRANCHED-CHAIN AMINO 12 p12.1 856c ENST00000334327 ACID AMINOTRANSFERASE, CYTOSOLIC (EC 2.6.1.42) (BCAT(C)) (ECA39 PROTEIN). [Source: SWISSPROT; Acc: P54687] CaMax: ENSMUSG00000022676 ENSMUST00000023356 ZINC FINGER PROTEIN 16 B1 863c SLUG (NEURAL CREST TRANSCRIPTION FACTOR SLUG) (SNAIL HOMOLOG 2). [Source: SWISSPROT; Acc: P97469] CaMax: ENSG00000175582 ENST00000310653 RAS-RELATED PROTEIN 11 q13.4 890a ENST00000334372 RAB-6A (RAB-6). [Source: SWISSPROT; Acc: P20340] CaMax: 8a CaMax: 905a CaMax: 906a CaMax: 907a CaMax: ENSG00000145730 ENST00000304400 PEPTIDYL-GLYCINE 5 q21.1 909a ENST00000304406 ALPHA-AMIDATING ENST00000282992 MONOOXYGENASE ENST00000325306 PRECURSOR (EC 1.14.17.3) ENST00000274392 (PAM). [Source: SWISSPROT; Acc: P19021] CaMax: ENSMUSG00000023944 ENSMUST00000024739 HEAT SHOCK PROTEIN HSP 17 C 90c 90-BETA (HSP 84) (TUMOR SPECIFIC TRANSPLANTATION 84 KDA ANTIGEN) (TSTA). [Source: SWISSPROT; Acc: P11499] CaMax: 911a CaMax: 911a CaMax: 912b CaMax: 914a CaMax: 914a CaMax: 915a CaMax: 915a CaMax: ENSG00000104177 ENST00000267836 MYELIN GENE 15 q21.1 919b ENST00000324324 EXPRESSION FACTOR 2. [Source: RefSeq; Acc: NM_016132] CaMax: 91f CaMax: 91f CaMax: ENSG00000104177 ENST00000267836 MYELIN GENE 15 q21.1 919b ENST00000324324 EXPRESSION FACTOR 2. [Source: RefSeq; Acc: NM_016132] CaMax: ENSG00000084676 ENST00000288599 NUCLEAR RECEPTOR 2 p23.3 92c ENST00000326011 COACTIVATOR 1 ISOFORM 1. [Source: RefSeq; Acc: NM_003743] CaMax: ENSG00000125953 ENST00000246165 CHURCHILL PROTEIN 14 q23.3 935b (MY015 PROTEIN). [Source: SWISSPROT; Acc: Q8WUH1] CaMax: 936b CaMax: 936b CaMax: ENSRNOG00000011175 4 q24 945a CaMax: 947a CaMax: 947a CaMax: ENSG00000144592 ENST00000316654 3 p25.1 949c ENST00000273079 CaMax: ENSMUSG00000021290 ENSMUST00000021719 6.8 KDA MITOCHONDRIAL 12 F2 953a PROTEOLIPID. [Source: SWISSPROT; Acc: P56379] CaMax: ENSG00000134644 ENST00000257075 PUMILIO HOMOLOG 1. 1 p35.2 963c [Source: RefSeq; Acc: NM_014676] CaMax: 96e CaMax: 981a CaMax: 984a CaMax: 984a CaMax: ENSG00000118971 ENST00000261254 G1/S-SPECIFIC CYCLIN D2. 12 p13.32 986a [Source: SWISSPROT; Acc: P30279] CaMax: ENSG00000125398 ENST00000245479 TRANSCRIPTION FACTOR 17 q24.3 990a SOX-9. [Source: SWISSPROT; Acc: P48436] CaMax: 992a CaMax: ENSG00000005700 ENST00000306270 INHIBITOR OF BRUTON'S 6 q14.1 994b TYRSOINE KINASE; BTK- BINDING PROTEIN. [Source: RefSeq; Acc: NM_015525] CaMax: ENSG00000008988 ENST00000009589 40S RIBOSOMAL PROTEIN 8 q12.1 996a S20. [Source: SWISSPROT; Acc: P17075]

TABLE 2B CaMax Gene Swissprot Sig. ID Ensemble OMIM RefSeq Pfam InterPro Pep. TMHMM HUGO CaMax: ENST00000244769 1002b CaMax: ENST00000244769 1002b CaMax: NM_178043 PF05383 IPR001199 1005a NM_032239 NM_018078 CaMax: TISD_HUMAN NM_006887 PF04553 IPR000571 ZFP36L2 1006b PF00642 IPR007635 CaMax: TISD_HUMAN NM_006887 PF04553 IPR000571 ZFP36L2 1007a PF00642 IPR007635 CaMax: ENST00000245479 1008a CaMax: ENST00000245479 1008a CaMax: GDC_HUMAN 139080 NM_152707 PF00153 IPR001993 SLC25A16 1009c IPR002167 IPR002067 CaMax: trembl|AB012223_1 1011a CaMax: Transcript: 1011a ENSRNOT00000033408 CaMax: ENST000000326567 1013a CaMax: NM_018359 1015d CaMax: Transcript: 1016b ENST00000330345 CaMax: Z333_HUMAN NM_032433 PF01352 IPR007087 1019a PF00096 IPR007086 IPR001909 CaMax: CGRR_HUMAN 114190 NM_005795 PF02793 IPR000832 Sigp Tmhmm CALCRL 1020a PF00002 IPR003287 IPR003289 IPR001688 IPR001879 CaMax: trembl|AB012223_1 1026b CaMax: Transcript: 1026b ENSRNOT00000035961 CaMax: trembl|HSRBP1_1 1028c CaMax: ENST00000260780 1028c CaMax: NM_145702 PF04218 IPR004875 TIGD1 1029a PF03184 IPR006695 CaMax: ENST00000287239 103a CaMax: PPO3_HUMAN 607726 NM_005485 PF05406 IPR001290 ADPRTL3 1044c PF02877 IPR004102 PF00644 CaMax: ROH1_HUMAN 601035 NM_005520 PF00076 IPR000504 HNRPH1 104a CaMax: ENST00000322598 1050a CaMax: ENST00000261710 1054a CaMax: trembl|AB012223_1 1057b CaMax: pironly|S72489 1060a CaMax: PF02008 IPR002857 1061a CaMax: ENST00000277359 1063b CaMax: FRIH_HUMAN 134770 NM_002032 PF00210 IPR001519 FTH1 106a CaMax: Transcript: 1070b ENST00000322595 CaMax: trembl|HS09953_1 1072a CaMax: ENST00000295955 1072a CaMax: gpnew|37790758 1089d CaMax: ENST00000297846 108a CaMax: swiss|ATP6_CANFA 1090d CaMax: gpnew|37790758 1094b CaMax: ENSMUST00000006525 1094b CaMax: NM_019974 PF00089 IPR001254 Sigp Prss20- 1095a NM_133712 IPR001314 pending 2300002A1 3Rik CaMax: NM_019974 PF00089 IPR001254 Sigp Prss20- 1096a NM_133712 IPR001314 pending 2300002A1 3Rik CaMax: NM_014796 1098a CaMax: NM_032202 IPR001969 109a CaMax: RB14_HUMAN NM_016322 PF00071 IPR001687 RAB14 1105a IPR001806 CaMax: NM_152388 Tmhmm ALS2CR4 1106a CaMax: SR13_HUMAN NM_052851 PF00620 IPR001687 STARD13 1108a PF01852 IPR000198 IPR002913 CaMax: gpnew|37790758 1110b CaMax: gpnew|37790758 1110b CaMax: SES1_HUMAN 606103 NM_014454 PF04636 IPR006730 SESN1 1111b CaMax: NM_032042 IPR000886 Sigp 1112a IPR001472 CaMax: Transcript: 111a ENST00000327492 CaMax: NM_022130 PF05719 GOLPH3 1120a CaMax: IPR000566 1121a CaMax: gpnew|37790758 1131b CaMax: trembl|PM43360_1 1132a CaMax: MEFC_HUMAN 600662 NM_002397 PF00319 IPR002100 MEF2C 1134a CaMax: FXP2_HUMAN 605317 NM_148898 PF00904 IPR007087 FOXP2 1135a 602081 NM_148899 PF00250 IPR001766 NM_148900 IPR000354 NM_014491 CaMax: ENST00000256429 1137b CaMax: ENST00000261765 1138a CaMax: ENST00000245479 1139a CaMax: CA1E_HUMAN 120325 NM_001855 PF02210 IPR008160 Sigp COL15A1 1145a PF01391 IPR003129 IPR001791 CaMax: CA1E_HUMAN 1145a CaMax: ENST00000308148 1146a CaMax: ENST00000296084 1159b CaMax: ROH1_HUMAN 601035 NM_005520 PF00076 IPR000504 HNRPH1 104a CaMax: TPM1_HUMAN 191010 NM_000366 PF00261 IPR000533 TPM1 1169b CaMax: DYHC_HUMAN 600112 NM_001376 PF03028 IPR001687 DNCH1 1177c IPR000169 IPR004273 CaMax: TIAM_HUMAN 600687 NM_003253 PF00169 IPR001331 TIAM1 1184a PF02196 IPR001849 PF00595 IPR001478 PF00621 IPR000219 IPR003116 IPR001472 CaMax: TIAM_HUMAN 1184a CaMax: PF02269 IPR003195 1190b CaMax: PF02269 IPR003195 1192b CaMax: ENST00000307407 11b CaMax: swiss|UB15_HUMAN 120a CaMax: ENST00000280377 120a CaMax: ENST00000235420 1212b CaMax: VAV3_HUMAN 605541 NM_006113 PF00307 IPR002086 VAV3 1213d PF00621 IPR002219 PF00169 IPR001331 PF00130 IPR000980 PF00017 IPR001452 PF00018 IPR003096 IPR001849 IPR001715 IPR000219 CaMax: ENST00000305327 1217a CaMax: Transcript: 1220b ENST00000333521 CaMax: ENST00000244769 1226d CaMax: ENST00000244769 1226d CaMax: trembl|AY027883_1 123c CaMax: ENST00000313779 123c CaMax: WDR3_HUMAN 604737 NM_006784 PF00400 IPR001680 WDR3 1243a PF04003 IPR007148 CaMax: ENST00000319046 1245b CaMax: NM_018359 1246a CaMax: ENST00000263196 1248b CaMax: NM_018359 1253a CaMax: trembl|BC043468_1 1257b CaMax: Genscan: 1257b AC073655.26.1.188105.67776.86719 CaMax: ENST00000325918 1260c CaMax: PF00036 IPR002048 1263b IPR000694 CaMax: PCCA_HUMAN 232000 NM_000282 PF00289 IPR001882 PCCA 1267a 606054 PF02786 IPR005479 PF02785 IPR005481 PF00364 IPR000089 IPR005482 CaMax: PCCA_HUMAN 232000 NM_000282 PF00289 IPR001882 PCCA 1267a 606054 PF02786 IPR005479 PF02785 IPR005481 PF00364 IPR000089 IPR005482 CaMax: NM_152520 PF00096 IPR007087 1270a CaMax: S24A_HUMAN 607183 PF04810 IPR007123 SEC24A 1272a PF04811 IPR006895 PF04815 IPR006896 PF00626 IPR006900 IPR000694 CaMax: trembl|AB012223_1 1273b CaMax: trembl|AB012223_1 1276a CaMax: trembl|AY027883_1 127b CaMax: ENST00000313779 127b CaMax: Genscan: 1282b CAAA01209745.1.1.24557.3159.16476 CaMax: ENSRNOT00000023862 1284b CaMax: NM_133433 1287c NM_015384 CaMax: NM_133433 1288a NM_015384 CaMax: HS9B_MOUSE NM_008302 PF02518 IPR001404 Hspcb 128a PF00183 IPR003594 CaMax: KU86_HUMAN 194364 NM_021141 PF03731 IPR006164 XRCC5 1292c PF02735 IPR005160 PF03730 IPR005161 CaMax: SYEP_HUMAN 138295 NM_004446 PF00749 IPR001589 EPRS 1294b PF03950 IPR001412 PF00458 IPR000738 PF00587 IPR000924 PF03129 IPR002316 PF00043 IPR004046 IPR002314 IPR004154 CaMax: NM_014991 PF02138 IPR001680 WDFY3 1299c NM_178583 PF00400 IPR000306 PF01363 IPR000409 CaMax: tremblnew| 129b AX400039_1 CaMax: ENST00000265677 129b CaMax: ENST00000288263 12a CaMax: PF00023 IPR002110 1301a CaMax: 607958 NM_014178 STXBP6 1304a CaMax: trembl|AB012223_1 1308c CaMax: ENST00000297641 1308c CaMax: ENSRNOT00000011463 130b CaMax: ENSRNOT00000024354 1316b CaMax: LIN1_HUMAN 1318a CaMax: LIN1_HUMAN 1320 CaMax: OGT1_RAT PF00515 IPR001440 1322c CaMax: trembl|HS09953_1 1323br CaMax: ENST00000295955 1323br CaMax: trembl|HS09953_1 1324a CaMax: ENST00000295955 1324a CaMax: pironly|B34087 1335b CaMax: ENST00000321183 1335b CaMax: 603054 NM_013372 PF03045 IPR004133 Sigp CKTSF1B1 1341a IPR001472 CaMax: LIN1_NYCCO 1352b CaMax: NM_145702 PF04218 IPR004875 TIGD1 1354a PF03184 IPR006695 CaMax: trembl|AF318340_1 1355a CaMax: ENST00000324229 1355a CaMax: FUT8_HUMAN 602589 NM_178157 PF00018 IPR001452 Sigp Tmhmm FUT8 1361a NM_178154 IPR001472 NM_178155 NM_178156 NM_004480 CaMax: trembl|AB012223_1 1364d CaMax: ENST00000304487 1364d CaMax: CTGL_HUMAN 603399 NM_003881 PF00219 IPR001525 Sigp WISP2 1366a PF00093 IPR000867 PF00090 IPR001007 IPR000884 CaMax: NM_026140 PF00749 IPR001412 3230401I01Rik 1368a IPR000924 CaMax: 604785 NM_003798 PF01044 IPR001033 CTNNAL1 1371a IPR006077 CaMax: MPP8_HUMAN PF00385 IPR000953 137b PF00023 IPR002110 IPR001472 CaMax: trembl|S77350_1 1381a CaMax: ENST00000228938 1381a CaMax: 602942 NM_005665 PF00566 IPR001687 EVI5 1383a IPR000515 IPR000195 CaMax: ACOD_HUMAN 604031 NM_005063 PF00487 IPR001522 Tmhmm SCD 1384a IPR005804 CaMax: ENST00000222271 1391a CaMax: ENST00000256429 1394b CaMax: NM_181782 PF01476 IPR002482 NCOA7 1397b CaMax: ENST00000318060 1399a CaMax: ENST00000295709 13a CaMax: trembl|AB012223_1 1400a CaMax: NM_014247 PF00027 IPR000595 PDZGEF1 1401c PF00595 IPR001478 PF00788 IPR001895 PF00617 IPR000651 PF00618 IPR000159 CaMax: ENST00000231061 1403a CaMax: Transcript: 1406a ENST00000298992 CaMax: BAG5_HUMAN 603885 NM_004873 PF02179 IPR003103 BAG5 1409b CaMax: 602021 NM_002480 PF00023 IPR002110 PPP1R12A 1411a CaMax: Tmhmm 2900042B11Rik 1415b CaMax: Transcript: 1416a ENST00000336483 CaMax: ENST00000325584 1419a CaMax: trembl|BC018999_1 141c CaMax: Transcript: 141c ENST00000307901 CaMax: tremblnew| 142.1c AK001301_1 CaMax: ENST00000311713 142.1c CaMax: NM_004748 PF02987 IPR001687 Tmhmm 1420c NM_020739 IPR004238 CaMax: MLT1_HUMAN 604860 NM_006785 PF00531 IPR007110 MALT1 1421a NM_173844 PF00047 IPR000488 PF00656 IPR001309 CaMax: gpnew|37790758 1423b CaMax: SPL1_HUMAN 606041 NM_004684 PF00050 IPR002048 Sigp SPARCL1 143.2c IPR001999 IPR002350 CaMax: SPL1_HUMAN 606041 NM_004684 PF00050 IPR002048 Sigp SPARCL1 143.2c IPR001999 IPR002350 CaMax: Transcript: 1431a ENST00000296858 CaMax: trembl|AY157990_1 144.2a CaMax: ENST00000249297 144.2a CaMax: TIC3_HUMAN 607989 NM_016950 PF00050 IPR000716 Sigp Tmhmm SPOCK3 1448a PF00086 IPR002350 CaMax: Z271_HUMAN 604754 NM_006958 PF00096 IPR001687 ZNF271 1449a ZN16_HUMAN 601262 NM_003415 PF01352 IPR007087 ZNF16 Z268_HUMAN 606024 IPR007086 ZNF268 ZF64_HUMAN 604753 IPR000294 IPR001909 CaMax: C17_HUMAN 607930 NM_018659 Sigp 1450a CaMax: ENST00000261976 1452a CaMax: gp|34528169 1457b CaMax: P15_HUMAN 600503 NM_006713 PF02229 IPR003173 1459c IPR001472 CaMax: TCP4_HUMAN 1459c CaMax: RL10_HUMAN 312173 NM_006013 PF00826 IPR001197 RPL10 145b CaMax: trembl|HSU93567_2 1460a CaMax: ENST00000322543 1460a CaMax: trembl|BC049156_1 1461a CaMax: ENSMUST00000030311 1461a CaMax: trembl|AF325902_1 1466b CaMax: ENST00000222271 1466b CaMax: NM_023211 Tmhmm Usmg5 1469a CaMax: Y441_HUMAN NM_014797 PF00651 IPR007087 ZNF450 146b PF02178 IPR000345 PF00096 IPR007086 IPR000210 IPR000637 CaMax: NM_023211 Tmhmm Usmg5 1469a CaMax: ENST00000296084 1472a CaMax: CN4B_RAT 1475a CaMax: ID4_HUMAN 600581 NM_001546 PF00010 IPR001092 ID4 1476a IPR000694 CaMax: BTG2_HUMAN 601597 NM_006763 PF01211 IPR002087 BTG2 1477a CaMax: ENST00000317517 147b CaMax: HXA3_HUMAN 142954 NM_030661 PF00046 IPR001356 HOXA3 1481c NM_153631 IPR001827 NM_153632 IPR002965 IPR000047 IPR000694 CaMax: NM_017880 IPR000169 1482a CaMax: UTRO_HUMAN 1484b CaMax: ROA2_HUMAN 600124 NM_002137 PF00076 IPR000504 HNRPA2B1 1488b NM_031243 CaMax: ENST00000271717 148a CaMax: swiss|SEC3_HUMAN 1497c CaMax: ENST00000317675 1497c CaMax: ENST00000322519 1500b CaMax: ENST00000278824 1504d CaMax: trembl|AY061884_1 1506d CaMax: ENST00000229488 1506d CaMax: LB4D_HUMAN 601274 NM_012212 PF00107 IPR002085 LTB4DH 150a CaMax: NM_017880 IPR000169 1516a CaMax: gp|37589039 1519a CaMax: ENST00000311733 1519a CaMax: ENST00000281131 151b CaMax: trembl|AY267013_1 1520a CaMax: ENST00000261435 1520a CaMax: NM_016147 IPR000734 1521b IPR003089 IPR000639 IPR000379 CaMax: trembl|AY154463_1 1522b CaMax: trembl|AY154463_1 1531c CaMax: trembl|BC038422_1 1532a CaMax: ENST00000272761 1532a CaMax: Y373_HUMAN NM_014684 PF02524 IPR001687 1534b NM_025114 IPR003900 CaMax: Y373_BOVIN 1534b CaMax: ENST00000277895 1535a CaMax: 1541a CaMax: XCT_HUMAN 607933 NM_014331 PF00324 IPR004841 Tmhmm SLC7A11 1546b IPR002293 CaMax: ENST00000254926 1548c CaMax: ENST00000294618 1549a CaMax: NM_017658 PF00651 IPR000210 BTBD5 1551a CaMax: trembl|AB012223_1 1554c CaMax: NM_153689 Sigp 1573a CaMax: trembl|AB012223_1 1574b CaMax: ENST00000310739 1574b CaMax: 605861 NM_014255 IPR000886 Sigp TMEM4 1577a IPR008139 CaMax: gp|34535028 1578a CaMax: trembl|S77350_1 157b CaMax: ENST00000228938 157b CaMax: gp|34849666 1591a CaMax: Transcript: 1591a ENSRNOT00000010671 CaMax: ENSMUST00000060486 1594a CaMax: trembl|AF081111_2 1596b CaMax: Transcript: 1596b ENST00000319237 CaMax: LIN1_NYCCO 1598a CaMax: trembl|CSAAE_1 159a CaMax: Transcript: 159a ENST00000311190 CaMax: IPR000694 Sigp Tmhmm 15b CaMax: NM_018138 1602a CaMax: ENSDART00000024018 1604a CaMax: PF00076 IPR000504 1626c CaMax: ENST00000325761 1628d CaMax: tremblnew| 1629a BC021535_1 CaMax: ENST00000229238 1629a CaMax: tremblnew| 1630b BC021535_1 CaMax: ENST00000229238 1630b CaMax: NM_014683 PF00069 IPR000719 ULK2 1631d IPR002290 IPR001245 CaMax: NM_014683 PF00069 IPR000719 ULK2 1635a IPR002290 IPR001245 CaMax: NM_014683 PF00069 IPR000719 ULK2 1635a IPR002290 IPR001245 CaMax: pironly|B28096 1639a CaMax: Transcript: 1639a ENST00000329369 CaMax: NM_017967 163a CaMax: NM_015440 PF00763 IPR000559 FTHFSDC1 1646a PF02882 IPR000672 PF01268 CaMax: PF00629 IPR000998 Sigp 1648a CaMax: MI2B_HUMAN 139111 NM_002090 PF00048 IPR001089 CXCL3 164c IPR002473 IPR001811 CaMax: trembl|S57162_1 1659a CaMax: ENST00000316200 1659a CaMax: NM_017887 PF05907 166a CaMax: trembl|AB012223_1 1671b CaMax: Transcript: 1671b ENST00000329369 CaMax: ENST00000321491 1675a CaMax: trembl|AF081104_2 1676a CaMax: ENST00000299933 1676a CaMax: ENST00000307746 1678a CaMax: ENSRNOT00000015118 1682a CaMax: RL32_HUMAN 168c CaMax: CX41_RAT NM_017202 PF02936 IPR004203 Tmhmm 1690a CaMax: NM_018199 PF01612 IPR000345 C14orf114 1691b IPR002562 CaMax: CX41_RAT NM_017202 PF02936 IPR004203 Tmhmm 1692a CaMax: FGR2_HUMAN 176943 NM_022971 PF00047 IPR000719 Sigp Tmhmm FGFR2 1693b BFR2_HUMAN 101200 NM_022974 PF00069 IPR001245 101600 NM_022976 IPR007110 123150 NM_022969 123500 NM_022972 NM_022973 NM_000141 NM_023028 NM_023029 NM_022975 NM_022970 NM_023031 NM_023030 CaMax: gp|37589132 1696a CaMax: ENST00000259146 1696a CaMax: ENST00000303924 16b CaMax: CAR6_HUMAN NM_032587 PF00619 IPR001687 CARD6 1705a IPR001315 IPR001472 CaMax: Genscan: 1709a AC091966.3.1.91296.20868.46788 CaMax: NM_018227 PF00899 IPR000594 1714a PF02134 IPR000127 IPR000205 CaMax: ENST00000299230 1715a CaMax: NM_033296 1717a CaMax: ILEU_HUMAN 130135 NM_030666 PF00079 IPR000215 SERPINB1 1721a IPR001472 CaMax: GOA4_HUMAN 602509 NM_002078 PF00904 IPR006162 GOLGA4 1722a 270150 PF01465 IPR001990 IPR000354 IPR000237 IPR001472 CaMax: NM_153832 PF00001 IPR000276 Tmhmm 1724a NM_007369 CaMax: ENST00000026952 1725a CaMax: trembl|AB012223_1 1726a CaMax: ENST00000325761 1726a CaMax: 606101 NM_032571 PF01825 IPR000152 Sigp Tmhmm 1727a NM_152939 PF00002 IPR001881 PF00008 IPR001740 IPR000832 IPR003056 IPR006209 IPR000203 CaMax: ENST00000222271 1730a CaMax: ENST00000318296 1738b CaMax: ENST00000221700 1741a CaMax: LGR4_HUMAN 606666 NM_018490 PF01462 IPR007087 Sigp Tmhmm GPR48 1744a PF00560 IPR002131 PF00001 IPR000276 IPR001611 IPR000372 CaMax: LGR4_HUMAN 1744a CaMax: T2FB_HUMAN 189969 NM_004128 PF02270 IPR003196 GTF2F2 174a CaMax: T2FB_HUMAN 174a CaMax: ENST00000282228 1750a CaMax: ENST00000319353 1751a CaMax: trembl|AK051102_1 1755a CaMax: Genscan: 1755a AL109926.9.1.114298.7096.114020 CaMax: RU17_HUMAN 180740 NM_003089 PF00076 IPR000504 SNRP70 1758a CaMax: NM_017658 PF00651 IPR000210 BTBD5 1759b CaMax: trembl|AX648027_1 1760c CaMax: ENST00000326555 1760c CaMax: ENSMUST00000053459 1772a CaMax: GCC1_HUMAN 607418 NM_024523 PF01465 IPR000237 GCC1 1775a CaMax: GCC1_HUMAN 607418 NM_024523 PF01465 IPR000237 GCC1 1775a CaMax: Transcript: 1778c ENST00000315390 CaMax: Sigp Tmhmm 1782b CaMax: 189889 NM_005653 PF04516 IPR007604 TFCP2 178a IPR001472 CaMax: gp|34527509 1794a CaMax: ENST00000310739 1794a CaMax: trembl|AB012223_1 17a CaMax: ENST00000320480 1800a CaMax: CLPX_HUMAN NM_006660 PF00004 IPR001687 Sigp CLPX 1801b IPR000345 IPR003959 CaMax: NM_145702 PF04218 IPR004875 TIGD1 180a PF03184 IPR006695 CaMax: NM_025082 IPR001472 1810a CaMax: pironly|B34087 1811b CaMax: SIL6_HUMAN 604405 NM_001245 PF00047 IPR003006 Sigp Tmhmm SIGLEC6 1812b IPR007110 IPR001472 CaMax: AMD_HUMAN 170270 NM_000919 PF01082 IPR002086 Sigp Tmhmm PAM 1814c NM_138766 PF03712 IPR000323 NM_138822 PF01436 IPR000720 NM_138821 IPR001258 CaMax: AMD_BOVIN 1814c CaMax: ENST00000324450 1818a CaMax: PLK_MOUSE NM_013500 PF00047 IPR000538 Sigp Crtl1 1828b PF00193 IPR003006 CaMax: trembl|AY293286_1 1834b CaMax: gpnew|37790758 1849d CaMax: Transcript: 1852a ENST00000333606 CaMax: Sigp 1853a CaMax: CYB5_RAT NM_022245 PF00173 IPR001199 Tmhmm 1857c CaMax: 606833 NM_170606 PF02178 IPR000194 MLL3 1859a NM_021230 PF00904 IPR000345 PF00628 IPR000637 PF00505 IPR000910 PF05964 IPR001965 PF05965 IPR001214 PF00856 IPR000354 IFR001472 IPR000694 CaMax: swiss|PEN2_HUMAN 1863c CaMax: ENST00000222266 1863c CaMax: NM_133953 IPR003006 1810061H24Rik 1864b CaMax: NM_014945 PF00412 IPR001781 186a PF02209 IPR003128 CaMax: trembl|AX648027_1 1874b CaMax: ENST00000326555 1874b CaMax: trembl|AX648027_1 1879a CaMax: ENST00000326555 1879a CaMax: ENST00000253814 1881b CaMax: NM_021927 PF00009 IPR001687 1894a PF03144 IPR000795 PF00679 IPR001806 IPR000640 IPR004161 CaMax: trembl|AB012223_1 18a CaMax: trembl|BC019022_1 1912a CaMax: ENST00000318072 1912a CaMax: swiss|COG1_HUMAN 1913a CaMax: ENST00000299886 1913a CaMax: NM_173082 PF00176 IPR000345 SHPRH 1917f PF00538 IPR001841 PF00628 IPR000330 PF00271 IPR001650 IPR005818 IPR001965 CaMax: NM_080927 PF00431 IPR000859 Tmhmm 1919a PF03815 IPR000421 PF00754 IPR004043 CaMax: 1920a CaMax: ENSMUST00000041864 1928a CaMax: Y539_HUMAN C21orf108 1929c CaMax: PF00168 IPR000008 Tmhmm 1930a CaMax: 604934 NM_003193 PF01302 IPR001611 TBCE 1940e PF00560 IPR000938 CaMax: 606105 NM_022109 PF04515 IPR007603 Sigp Tmhmm 1941e NM_080546 CaMax: 605889 NM_014476 PF00595 IPR001781 1943a PF00412 IPR001478 CaMax: trembl|AK025270_1 1944a CaMax: ENST00000319557 1944a CaMax: gpnew|37748505 1945a CaMax: ENST00000312037 1945a CaMax: gpnew|37748505 1948b CaMax: ENST00000312037 1948b CaMax: gp|37590686 1949a CaMax: ENST00000320480 1949a CaMax: VAV3_HUMAN 605541 NM_006113 PF00307 IPR002086 VAV3 1950a PF00621 IPR002219 PF00169 IPR001331 PF00130 IPR000980 PF00017 IPR001452 PF00018 IPR003096 IPR001849 IPR001715 IPR000219 CaMax: NAB1_HUMAN 600800 NM_005966 PF04904 IPR006986 NAB1 1953a PF04905 IPR006988 PF04902 IPR006989 CaMax: ENST00000321787 1954e CaMax: MADI_HUMAN 603755 NM_007323 PF01363 IPR000345 MADHIP 1961e NM_004799 IPR000306 NM_007324 CaMax: TAP2_HUMAN 170261 NM_000544 PF00664 IPR001687 Sigp Tmhmm TAP2 1967a NM_018833 PF00005 IPR003439 IPR001140 CaMax: NM_020651 PF04710 IPR006800 PELI1 1968a CaMax: CA1B_HUMAN 120280 NM_080629 PF02210 IPR001687 Sigp COL11A1 1982a 604841 NM_080630 PF01391 IPR001230 154780 NM_001854 PF01410 IPR008160 IPR000885 IPR003129 IPR001791 CaMax: trembl|AB030650_1 1989b CaMax: 605789 NM_014268 PF00307 IPR001715 MAPRE2 1990a PF03271 IPR004953 CaMax: ENST00000244096 1991d CaMax: ENST00000322438 1a CaMax: ENSMUST00000034996 2002c CaMax: NM_018364 IPR001472 2003a IPR000694 CaMax: NM_029522 PF00515 IPR001440 Pins- 2008a PF02188 IPR003109 pending CaMax: RI14_HUMAN 602490 NM_003489 IPR001687 NRIP1 2013a CaMax: ENSMUST00000028222 2014f CaMax: RL4_HUMAN 180479 NM_000968 PF00573 IPR002086 RPL4 2015e IPR002136 IPR001472 CaMax: M4K3_HUMAN 604921 NM_003618 PF00069 IPR000719 MAP4K3 2020b PF00780 IPR001180 CaMax: M4K3_MOUSE 2020b CaMax: NM_015589 PF00536 IPR001660 Sigp SAMD4 2022a CaMax: trembl|BT008100_1 2023b CaMax: ENST00000312547 2023b CaMax: ENST00000314543 2024a CaMax: NM_178352 IPR003267 2034a CaMax: RPCZ_HUMAN 606007 NM_016310 PF02150 IPR001222 POLR3K 2035d PF01096 IPR001529 CaMax: ENST00000276230 204a CaMax: HELZ_HUMAN 606699 NM_014877 PF00642 IPR001687 HELZ 2056d IPR000571 CaMax: ENST00000282218 2059b CaMax: ENST00000276230 205a CaMax: NM_016081 PF00047 IPR000634 2070a IPR007110 IPR002965 IPR000694 CaMax: trembl|AB012223_1 2073b CaMax: Transcript: 2073b ENST00000320621 CaMax: A8A1_HUMAN NM_006095 PF00702 IPR001687 Tmhmm ATP8A1 2074b PF00122 IPR001757 IPR008250 IPR005834 CaMax: NM_178043 PF05383 IPR001199 2075a NM_032239 NM_018078 CaMax: ENST00000324643 2076c CaMax: SEP7_HUMAN 603151 NM_001788 PF00735 IPR001687 CDC10 2078a IPR000038 CaMax: NM_020830 PF00400 IPR001680 WDFY1 2083e NM_178350 PF01363 IPR000306 CaMax: NM_182543 PF01189 IPR001678 2088a CaMax: gpnew|37790758 2092c CaMax: ENST00000258969 2095a CaMax: swissnew| 2099a SF30_HUMAN CaMax: ENST00000239010 2099a CaMax: trembl|BC001284_1 20a CaMax: ENST00000318446 20a CaMax: FBN1_HUMAN 134797 NM_000138 PF00008 IPR000152 Sigp FBN1 2100b 154700 PF00683 IPR006209 IPR007087 IPR001881 IPR001438 IPR002212 CaMax: ENST00000319412 2105a CaMax: Transcript: 2108b ENST00000314393 CaMax: ENST00000324450 2109a CaMax: Z345_HUMAN NM_003419 PF00096 IPR007087 ZNF345 2110a IPR007086 CaMax: ENST00000324450 2113a CaMax: MRP1_HUMAN 158343 NM_004996 PF00664 IPR001687 Tmhmm ABCC1 211b NM_019901 PF00005 IPR000719 NM_019902 IPR003439 NM_019898 IPR001140 NM_019862 NM_019900 NM_019899 CaMax: ENST00000321873 2122a CaMax: NM_145648 PF00854 IPR001117 Tmhmm SLC15A4 2123a IPR000109 CaMax: NM_020239 PF00786 IPR000095 2129a CaMax: ENST00000175091 2132a CaMax: ENST00000325604 2135d CaMax: ENST00000294665 2136b CaMax: ENSMUST00000000642 2141a CaMax: Genscan: 2142a CAAA01004319.1.1.45274.2016.41736 CaMax: ENST00000285599 2160a CaMax: NM_178043 PF05383 IPR001199 2161c NM_032239 NM_018078 CaMax: ENST00000244769 2165a CaMax: ENST00000278483 2167a CaMax: ENST00000309655 2189b CaMax: ENSMUST00000000642 2198b CaMax: ENST00000244769 2201a CaMax: ENST00000244769 2201a CaMax: ENST00000274054 2205a CaMax: ENST00000244769 2210a CaMax: PF00168 IPR000008 Tmhmm 2222b CaMax: Transcript: 2223a ENST00000228330 CaMax: 604283 NM_005807 PF01033 IPR000585 Sigp PRG4 2224a PF05001 IPR001212 PF02818 IPR002965 PF00045 IPR004168 IPR000684 IPR001472 CaMax: PF01436 IPR001258 2225b IPR006663 CaMax: TRFR_MOUSE NM_013696 PF00001 IPR000276 Tmhmm Trhr 2234a IPR002120 CaMax: ENST00000296412 2235a CaMax: ENST00000296412 2235a CaMax: CN3A_HUMAN 123805 NM_000921 PF00233 IPR002073 Tmhmm PDE3A 2238a IPR005829 IPR001917 CaMax: CN3A_HUMAN 123805 NM_000921 PF00233 IPR002073 Tmhmm PDE3A 2241a IPR005829 IPR001917 CaMax: CN3A_HUMAN 123805 NM_000921 PF00233 IPR002073 Tmhmm PDE3A 2238a IPR005829 IPR001917 CaMax: trembl|HSF8L1B_1 224a CaMax: swiss|LIN1_NYCCO 2251d CaMax: NM_018359 2252b CaMax: ENST00000245479 2258a CaMax: ENST00000245479 2258a CaMax: ENST00000245479 2258a CaMax: gp|37361816 225a CaMax: ENSMUST00000000642 2264b CaMax: ENSMUST00000000642 2264b CaMax: ENST00000306715 2266b CaMax: TSP1_HUMAN 188060 NM_003246 PF02210 IPR006209 Sigp THBS1 2267a PF00093 IPR001007 PF00090 IPR000884 PF00008 IPR003129 PF02412 IPR003367 PF05735 IPR001791 CaMax: ENST00000317584 231a CaMax: ENST00000296412 2331c CaMax: 2341b CaMax: ENST00000319965 2351c CaMax: ENST00000319965 2351c CaMax: CN3A_HUMAN 123805 NM_000921 PF00233 IPR002073 Tmhmm PDE3A 2241a IPR005829 IPR001917 CaMax: Genscan: 235a RNOR01069968.11947.48582 CaMax: TSP1_HUMAN 188060 NM_003246 PF02210 IPR006209 Sigp THBS1 2374a PF00093 IPR001007 PF00090 IPR000884 PF00008 IPR003129 PF02412 IPR003367 PF05735 IPR001791 CaMax: Genscan: 238a AC016601.7.1.145264.1553.20016 CaMax: SPCN_HUMAN 182810 NM_003127 PF00435 IPR002048 SPTAN1 239a PF00018 IPR000276 PF00036 IPR001452 IPR002017 CaMax: GME1_HUMAN 604409 NM_006582 PF01342 IPR000770 GMEB1 23a NM_024482 CaMax: NM_032811 PF05964 240a PF05965 CaMax: trembl|AB012223_1 243a CaMax: NM_144972 PF00056 IPR001557 245a PF02866 IPR001236 IPR000205 IPR000594 CaMax: NM_018211 PF00076 IPR000504 248a IPR001064 CaMax: ENST00000239392 24a CaMax: gpnew|37790758 258a CaMax: gp|37361850 261c CaMax: ENST00000322543 261c CaMax: TENA_HUMAN 187380 NM_002160 PF00008 IPR006209 Sigp Tmhmm TNC 267d PF00041 IPR002049 PF00147 IPR003961 IPR002181 CaMax: NM_018696 PF00753 IPR001279 ELAC1 272d CaMax: ENSRNOT00000006484 27a CaMax: Genscan: 28s NA26110.1.701.1515 CaMax: YCE7_HUMAN NM_016077 PF01981 IPR002833 Sigp Tmhmm 307b CaMax: 180069 NM_000329 PF03055 IPR004294 RPE65 308c CaMax: M172_MOUSE 310h CaMax: ENST00000315874 311c CaMax: Genscan: 313a AL136225.8.1.42171.4910.17211 CaMax: ENST00000303575 314a CaMax: ENSRNOT00000022117 319b CaMax: SEC3_HUMAN 607879 NM_018261 320a NM_178237 CaMax: SEC3_HUMAN 320a CaMax: ENSRNOT00000022117 322a CaMax: NM_020935 PF00443 IPR001394 USP37 324a PF02809 IPR003903 CaMax: SPC4_MOUSE NM_019951 PF00461 IPR000508 Sigp Tmhmm Spc18- 326e IPR001733 pending CaMax: gp|37360062 327f CaMax: ENST00000315821 327f CaMax: NM_016081 PF00047 IPR000634 328b IPR007110 IPR002965 IPR000694 CaMax: 336a CaMax: trembl|BC024093_1 33a CaMax: ENSRNOT00000006836 33a CaMax: swiss|PTN3_HUMAN 340a CaMax: ENST00000262539 340a CaMax: trembl|AK033094_1 343b CaMax: ENST00000269073 343b CaMax: gp|34534817 34a CaMax: ENST00000316410 34a CaMax: FRIH_HUMAN 134770 NM_002032 PF00210 IPR001519 FTH1 106a CaMax: FRIH_HUMAN 134770 NM_002032 PF00210 IPR001519 FTH1 106a CaMax: tremblnew| 360a AK094461_1 CaMax: ENST00000291220 360a CaMax: EWS_HUMAN 133450 NM_005243 PF00076 IPR001064 EWSR1 364a NM_013986 PF00641 IPR000504 IPR001876 CaMax: COX1_CANFA 370a CaMax: A32B_HUMAN NM_006401 PF00560 IPR001611 ANP32B 374a CaMax: COX1_CANFA 375d CaMax: ENST00000278407 379a CaMax: 607686 NM_030917 PF05182 IPR007854 FIP1L1 38a CaMax: ENST00000293648 391a CaMax: tremblnew| 392a BC034135_1 CaMax: ENST00000319311 392a CaMax: trembl|BC051886_1 395a CaMax: ENST00000323751 395a CaMax: ALU7_HUMAN 397b CaMax: 3c CaMax: swiss|COX3_CANFA 406a-r CaMax: Transcript: 406a-r :ENST00000332194 CaMax: ALU1_HUMAN 408a CaMax: ALU1_HUMAN 409a CaMax: IF2A_HUMAN 603907 NM_004094 PF00575 IPR003029 EIF2S1 415b CaMax: gpnew|37790758 421a CaMax: IPR000694 Sigp Tmhmm 43a CaMax: ENST00000239392 446f CaMax: trembl|AK019226_1 44c CaMax: ENST00000264258 44c CaMax: trembl|AK007837_1 45.1b CaMax: ENST00000314138 45.1b CaMax: tremblnew| 450a HSM805132_1 CaMax: ENST00000325086 450a CaMax: ENST00000218713 452a CaMax: trembl|BC028178_1 455c CaMax: ENST00000317856 455c CaMax: trembl|HSU93569_1 457c CaMax: NFT5_HUMAN 604708 NM_006599 PF00554 IPR000451 NFAT5 459a NM_138713 PF01833 IPR002909 NM_138714 IPR001472 NM_173214 NM_173215 CaMax: swissnew| 461a SF30_HUMAN CaMax: ENST00000239010 461a CaMax: PURA_HUMAN 103060 NM_001126 PF00709 IPR001114 ADSS 464b CaMax: NM_016952 PF00047 IPR003961 Tmhmm CDON 465b PF00041 IPR007110 CaMax: ENST00000282493 46a CaMax: tremblnew| 472a BC019810_1 CaMax: ENST00000327301 472a CaMax: TCTL_HUMAN 300302 NM_006520 PF03645 IPR005334 TCTE1L 478a CaMax: TCTL_HUMAN 300302 NM_006520 PF03645 IPR005334 TCTE1L 479c CaMax: Genscan: 482a AP005117.2.1.148790.13386.95160 CaMax: ARH2_HUMAN 607560 NM_004723 PF00130 IPR002219 ARHGEF2 487a PF00621 IPR001849 PF00169 IPR000219 CaMax: HXK2_HUMAN 601125 NM_000189 PF00349 IPR001312 HK2 488a PF03727 CaMax: trembl|AK019226_1 48b CaMax: ENST00000264258 48b CaMax: trembl|AK088660_1 490c CaMax: ENSRNOT00000025796 490c CaMax: trembl|HSAB461_1 494a CaMax: ENST00000324722 494a CaMax: ENSRNOT00000011463 498a CaMax: swiss|RL31_HUMAN 50.1c CaMax: ENST00000264258 50.1c CaMax: ENSMUST00000050981 501b CaMax: ENST00000267434 504a CaMax: ENST00000248673 505b CaMax: ENSRNOT00000016310 507a CaMax: Transcript: 516c ENST00000328854 CaMax: Transcript: 517c ENST00000328854 CaMax: trembl|AY072691_1 51a CaMax: ENST00000321758 51a CaMax: NM_017658 PF00651 IPR000210 BTBD5 520a CaMax: MEFC_HUMAN 600662 NM_002397 PF00319 IPR002100 MEF2C 521b CaMax: ENST00000300162 523a CaMax: ENST00000242208 52a CaMax: PSA3_HUMAN 176843 NM_152132 PF00227 IPR000426 PSMA3 530b 176845 NM_002788 IPR001353 CaMax: ENST00000283629 538a CaMax: PF00069 IPR000719 539a IPR002290 IPR001245 CaMax: pironly|JU0033 540a CaMax: gp|34533874 543a CaMax: 605861 NM_014255 IPR000886 Sigp TMEM4 545a IPR008139 CaMax: NM_014827 PF00642 IPR000571 547c IPR001472 CaMax: NM_014827 PF00642 IPR000571 548c IPR001472 CaMax: 605975 NM_005839 PF01480 IPR002965 SRRM1 550a IPR002483 IPR001472 CaMax: ENST00000318468 552a CaMax: NM_031208 PF01557 IPR002529 553b CaMax: 605653 NM_012158 PF00646 IPR001810 FBXL3A 555b FBXL3B CaMax: tremblnew| 556b HSM805356_1 CaMax: NSF_HUMAN 557b CaMax: trembl|AF352051_1 558a CaMax: ENST00000319272 558a CaMax: RBB2_HUMAN 560b CaMax: ENST00000296499 561b CaMax: trembl|CFA388522_1 568a CaMax: ENST00000225430 568a CaMax: gpnew|38511552 56a CaMax: ENST00000202773 56a CaMax: EML4_HUMAN 607442 NM_019063 PF03451 IPR002048 EML4 571a PF00400 IPR001254 IPR001680 IPR000560 IPR005108 CaMax: ENST00000296412 574a CaMax: SFR6_HUMAN 601944 NM_006275 PF00076 IPR000504 SFRS6 579a IPR001472 CaMax: ITA6_HUMAN 147556 NM_000210 PF01839 IPR000413 Sigp Tmhmm ITGA6 57a 226730 PF00357 CaMax: NM_014553 PF04516 IPR007604 581a CaMax: PF00039 IPR006209 Fn1 583e PF00041 IPR000083 IPR002086 IPR003962 IPR003961 CaMax: ENST00000313783 58a CaMax: FALZ_HUMAN 601819 NM_182641 PF02791 IPR001687 FALZ 597c NM_004459 PF00628 IPR000345 PF00439 IPR001487 IPR006209 IPR001965 IPR004022 IPR000694 CaMax: swissnew|SMO2_MOUSE 59a CaMax: ENST00000230324 59a CaMax: Genscan: 609a RNOR01094784.3716.7206 CaMax: Transcript: 611a ENST00000256653 CaMax: gp|34532352 622a CaMax: Genscan: 622a AC107939.5.1.145264.83212.131724 CaMax: IQG1_HUMAN 603379 NM_003870 PF00307 IPR001936 IQGAP1 623a PF00397 IPR001202 PF00612 IPR001715 PF00616 IPR000048 PF03836 IPR000593 CaMax: ENSMUST00000058265 624b CaMax: trembl|BC046507_1 626a CaMax: ENST00000261631 626a CaMax: KRM1_HUMAN NM_153379 PF00431 IPR000859 Tmhmm KREMEN1□ 628a NM_032045 CaMax: 605975 NM_005839 PF01480 IPR002965 SRRM1 635a IPR002483 IPR001472 CaMax: TCTL_HUMAN 300302 NM_006520 PF03645 IPR005334 TCTE1L 638b CaMax: ENST00000309558 639a CaMax: trembl|AY259036_1 63a CaMax: Transcript: 63a ENST00000332194 CaMax: Y121_HUMAN 64.2a CaMax: U183_HUMAN NM_025187 PF03676 IPR005373 685a CaMax: ENST00000244411 690a CaMax: ENST00000244411 690a CaMax: NM_145702 PF04218 IPR004875 TIGD1 692a PF03184 IPR006695 CaMax: PF00443 IPR005479 697a IPR001394 CaMax: Z216_MOUSE 6b CaMax: NM_146000 IPR001472 D030060M11Rik 701a CaMax: 243305 NM_014425 PF00023 IPR002110 INVS 704b PF00612 IPR000048 CaMax: 243305 NM_014425 PF00023 IPR002110 INVS 704b PF00612 IPR000048 CaMax: ENST00000323467 70d CaMax: CA1A_HUMAN 120110 NM_000493 PF01391 IPR001073 Sigp COL10A1 710a 156500 PF00386 IPR008160 184250 CaMax: trembl|AK019226_1 711a CaMax: ENST00000264258 711a CaMax: trembl|BC008338_1 713a CaMax: ENST00000012559 713a CaMax: Genscan: 714a AL391495.16.1.142952.28457.34558 CaMax: ENST00000299020 718a CaMax: NU4M_CANFA 720a CaMax: PF00063 IPR001687 725a PF00612 IPR001609 IPR000048 CaMax: GDC_HUMAN 139080 NM_152707 PF00153 IPR001993 SLC25A16 726b IPR002167 IPR002067 CaMax: trembl|AK007442_1 72a CaMax: ENST00000250454 72a CaMax: trembl|HSDNAW_1 731a CaMax: ENST00000275603 731a CaMax: ATDA_HUMAN 313020 NM_002970 PF00583 IPR000182 SAT 736a CaMax: NM_133375 PF00773 IPR001900 739a CaMax: KE4_HUMAN 601416 NM_006979 PF02535 IPR002395 Sigp Tmhmm HKE4 73b IPR003689 CaMax: ENST00000315919 745a CaMax: NM_133433 747a NM_015384 CaMax: ENST00000294890 749a CaMax: ENSRNOT00000020282 74c CaMax: NM_025685 PF01410 IPR000885 5730512J02Rik 753b CaMax: trembl|AX704781_1 759b CaMax: ENST00000261981 759b CaMax: trembl|AK002413_1 764b CaMax: ENSRNOT00000005190 764b CaMax: IPR001687 765a CaMax: ENST00000325727 768a CaMax: ENST00000275248 76b CaMax: PRIO_HUMAN 176640 NM_000311 PF03991 IPR000817 Sigp Tmhmm PRNP 785b 123400 PF00377 600072 137440 603218 245300 606688 CaMax: ENSMUST00000029203 788a CaMax: Tmhmm NDFIP2 789a CaMax: SSPN_HUMAN 601599 NM_005086 Tmhmm SSPN 794a CaMax: NM_017812 PF05300 IPR007964 795a CaMax: Y379_HUMAN PF00023 IPR002110 810a CaMax: ENST00000222567 813a CaMax: Transcript: 815a ENST00000272273 CaMax: ENST00000252102 81a CaMax: trembl|AB012223_1 820a CaMax: ENST00000325761 820a CaMax: trembl|AX147999_1 827b CaMax: ENST00000269485 827b CaMax: ENST00000265264 828a CaMax: ENST00000252102 82b CaMax: trembl|AK019226_1 831a CaMax: ENST00000264258 831a CaMax: PF00039 IPR006209 Fn1 832a PF00041 IPR000083 IPR002086 IPR003962 IPR003961 CaMax: 607838 NM_032520 Sigp 833a CaMax: LIN1_NYCCO 835c CaMax: PF00400 IPR001680 839a CaMax: trembl|AY072691_1 841b CaMax: ENST00000321758 841b CaMax: trembl|AY170044_1 847a CaMax: NM_014301 PF01592 IPR002871 85.1c CaMax: Sigp Tmhmm 85.2b CaMax: Genscan: 850a AP000813.4.1.210816.38383.42179 CaMax: Genscan: 851a AP000813.4.1.210816.38383.42179 CaMax: BCAT_HUMAN 113520 NM_005504 PF01063 IPR001544 BCAT1 856c CaMax: SLUG_MOUSE NM_011415 PF00096 IPR007087 Snai2 863c IPR007086 CaMax: RB6A_HUMAN 179513 NM_002869 PF00071 IPR001687 RAB6A 890a IPR001806 CaMax: ENST00000254942 8a CaMax: ENST00000231061 905a CaMax: gpnew|37790758 906a CaMax: MANR_HUMAN 907a CaMax: AMD_HUMAN 170270 NM_000919 PF01082 IPR002086 Sigp Tmhmm PAM 909a NM_138766 PF03712 IPR000323 NM_138822 PF01436 IPR000720 NM_138821 IPR001258 CaMax: HS9B_MOUSE NM_008302 PF02518 IPR001404 Hspcb 90c PF00183 IPR003594 CaMax: trembl|AB012223_1 911a CaMax: ENST00000292530 911a CaMax: gp|34535483 912b CaMax: gp|34534229 914a CaMax: ENST00000273342 914a CaMax: swiss|ALU6_HUMAN 915a CaMax: ENST00000262877 915a CaMax: NM_016132 PF00076 IPR000504 MYEF2 919b CaMax: trembl|S78694_1 91f CaMax: ENST00000231004 91f CaMax: NM_016132 PF00076 IPR000504 MYEF2 919b CaMax: 602691 NM_147233 PF00010 IPR001092 NCOA1 92c NM_003743 PF00989 IPR000014 NM_147223 IPR001472 CaMax: CHUR_HUMAN NM_145165 IPR000345 C14orf52 935b CaMax: trembl|BT008233_1 936b CaMax: ENST00000316232 936b CaMax: PF00076 IPR000504 945a CaMax: trembl|AY310153_1 947a CaMax: ENSRNOT00000005605 947a CaMax: NM_152396 IPR001601 949c IPR000051 CaMax: 68MP_MOUSE NM_027360 Tmhmm 2010107E04Rik 953a CaMax: 607204 NM_014676 PF00806 IPR001313 PUM1 963c CaMax: RL32_HUMAN 96e CaMax: gpnew|37790758 981a CaMax: pironly|JC7185 984a CaMax: ENSMUST00000048377 984a CaMax: CGD2_HUMAN 123833 NM_001759 PF00134 IPR006671 CCND2 986a PF02984 IPR004367 CaMax: SOX9_HUMAN 114290 NM_000346 PF00505 IPR000910 SOX9 990a IPR001472 CaMax: tremblnew|AK096400_1 992a CaMax: 606457 NM_015525 PF00023 IPR001687 994b PF00415 IPR000405 PF00651 IPR002110 IPR000210 CaMax: RS20_HUMAN 603682 NM_001023 PF00338 IPR001687 RPS20 996a IPR001848

One embodiment of the invention relates to a combination comprising two or more polynucleotide molecules selected from SEQ ID NOs:1-1558, or fragments thereof. Preferably, the combination comprises about 10 or more polynucleotide molecules, more preferably about 50 or more polynucleotide molecules, more preferably about 200 or more polynucleotide molecules, more preferably about 400 or more polynucleotide molecules, more preferably about 1000 or more polynucleotide molecules.

In a preferred embodiment, the invention relates to a combination of 396 differentially expressed polynucleotide molecules, whose sequences are represented by SEQ ID NOs:1-396. Table 3 identifies a list of gene sequences determined from clinical samples to be differentially expressed in OA versus normal subjects to a degree that is statistically significant (p<0.05). Table 3 includes the gene IDs, expression values, standard deviations, and fold difference of expression (OA versus normal). Preferably, the combination comprises two or more of polynucleotide molecules selected from SEQ ID NOs:1-396 or fragments thereof.

In a particularly preferred embodiment, the invention relates to a combination of 217 differentially expressed polynucleotide molecules, whose sequences are represented by SEQ ID NOs:1-217. Table 4 identifies a list of gene sequences determined from clinical samples to be differentially expressed in OA versus normal subjects to a degree that is highly significant (p<0.01). Table 4 includes the gene IDs, expression values, standard deviations, and fold difference of expression (OA versus normal). Preferably, the combination comprises two or more of polynucleotide molecules selected from SEQ ID NOs:1-217 or fragments thereof.

According to an aspect of the invention, one or more oligonucleotide or polynucleotide probes for interrogating a sample may be prepared using the sequence information set forth herein for any of the 1558 isolated gene fragments (SEQ ID NOs:1-1558). According to another aspect of the invention, probes may be prepared using the sequence information available for any of the genes or gene fragments identified in. The probes should be of sufficient length to specifically hybridize substantially exclusively with appropriate complementary genes or transcripts. Preferably, the oligonucleotide probes will be at least about 10, 12, 14, 16, 18, 20 or 25 nucleotides in length. In some embodiments, longer probes of at least about 30, 40, 50, 60, 70, 80, 90 or 100 nucleotides are desirable, and probes longer than about 100 nucleotides may be suitable in some embodiments. Preferably, a collection of two or more nucleic acid probes for detecting expression of gene products differentially expressed in OA is provided, more preferably a collection of about 10 or more probes, more preferably a collection of about 50 or more probes, more preferably a collection of about 200 or more probes, more preferably a collection of about 400 or more probes, more preferably a collection of about 1000 or more probes.

In a preferred embodiment of the invention, one or more oligonucleotide or polynucleotide probes may be prepared using the sequence information set forth for any of SEQ ID NOs:1-396. Preferably, one or more oligonucleotide or polynucleotide probes may be prepared using the sequence information set forth for any of SEQ ID NOs:1-217.

In certain preferred embodiments of the present invention, immobilized nucleic acid probes may be used for the rapid and specific detection of nucleic acid molecules and their expression patterns. Typically, a nucleic acid probe is linked to a solid support and a target nucleic acid (e.g., a genomic nucleic acid, an amplicon, or, most commonly, an amplified mixture) is hybridized to the probe. Either the probe, or the target, or both, can be labeled, typically with a fluorophore or other tag, such as streptavidin. Where the target is labeled, hybridization may be detected by detecting bound fluorescence. Where the probe is labeled, hybridization is typically detected by quenching of the label. Where both the probe and the target are labeled, detection of hybridization is typically performed by monitoring a color shift resulting from proximity of the two bound labels. A variety of labeling strategies, labels, and the like, particularly for fluorescent based applications, are known in the art.

Another aspect of the invention relates to one or more probes comprising polypeptide binding agents that specifically bind to polypeptides produced by expression of one or more nucleic acid molecules comprising sequences selected from SEQ ID NOs:1-1558 or fragments thereof. According to another aspect of the invention, protein binding probes may be prepared using the sequence information available for any of the genes or gene fragments identified in Table 2. Preferably, a collection of two or more polypeptide probes for detecting expression of gene products differentially expressed in OA is provided, more preferably a collection of about 10 or more probes, more preferably a collection of about 50 or more probes, more preferably a collection of about 200 or more probes, more preferably a collection of about 400 or more probes, more preferably a collection of about 1000 or more probes.

In a preferred embodiment of the invention, probes comprising polypeptide binding agents specifically bind to polypeptides produced by nucleic acid molecules comprising sequences selected from SEQ ID NOs:1-396. In a particularly preferred embodiment, probes comprising polypeptide binding agents specifically bind to polypeptides produced by nucleic acid molecules comprising sequences selected from SEQ ID NOs:1-217.

Assay techniques that can be used to determine levels of a protein in a sample are also well known to those of skill in the art. Such assay methods include radioimmunoassays, competitive-binding assays, Western blot analysis and ELISA assays. In the assay methods utilizing antibodies, both polyclonal and monoclonal antibodies are suitable for use in the present invention. Such antibodies may be immunologically specific for a particular protein, or an epitope of the protein, or a protein fragment, as would be well understood by those of skill in the art. Methods of making polyclonal and monoclonal antibodies immunologically specific for a protein or peptide are also well known in the art.

Preferred embodiments of the present invention may utilize antibodies for the detection and quantification of proteins produced by expression of the polynucleotides described herein. Though proteins may be detected by immunoprecipitation, affinity separation, Western blot analysis and the like, a preferred method utilizes ELISA-type methodology wherein the antibody is immobilized on a solid support and a target protein or peptide is exposed to the immobilized antibody. Either the probe, or the target, or both, can be labeled. A variety of labeling strategies, labels, and the like, are known in the art.

In particularly preferred embodiments of the invention, expression patterns or profiles of a plurality of genes differentially expressed in osteoarthritis are observed utilizing arrays of probes for detecting target nucleic acids or proteins. In one embodiment, arrays of oligonucleotide or polynucleotide probes may be utilized, whereas another embodiment may utilize arrays of antibodies or other proteins that bind specifically to the differentially expressed gene products. Such arrays are commercially available (e.g., through Affymetrix, Inc., Applied Biosystems, Inc., Agilent, Inc.), or they may be custom made according to known methods, such as, for example, in-situ synthesis on a solid support or attachment of pre-synthesized probes to a solid support via micro-printing techniques. In preferred embodiments, arrays of nucleic acid or protein-binding probes are custom made to specifically detect transcripts or proteins produced by two or more of the 1558 differentially expressed genes or gene fragments described herein. In one embodiment of the invention, arrays of nucleic acid or protein-binding probes are custom made to specifically detect transcripts or proteins produced by two or more of the genes or gene fragments identified in Table 2. In a preferred embodiment, arrays of nucleic acid or protein-binding probes are custom made to specifically detect transcripts or proteins produced by two or more of the 396 differentially expressed genes or gene fragments identified in Table 3. In a preferred embodiment, arrays of nucleic acid or protein-binding probes are custom made to specifically detect transcripts or proteins produced by two or more of the 217 differentially expressed genes or gene fragments identified in Table 4.

Preferably, a collection of two or more nucleic acid or polypeptide probes for detecting expression of gene products differentially expressed in OA is immobilized on a support in discrete locations, more preferably a collection of about 10 or more probes, more preferably a collection of about 50 or more probes, more preferably a collection of about 200 or more probes, more preferably a collection of about 400 or more probes, more preferably a collection of about 1000 or more probes.

Since chondrocytes represent the cellular component of cartilage, a tissue affected by OA, the construction of a chondrocyte array may represent a powerful tool to study the gene expression profile of osteoarthritic chondrocytes. The use of differential display for transcript selection was used by the present inventors to enrich the clones represented on an array for transcripts associated with OA.

In one aspect of the invention, methods are provided for assaying OA-associated nucleic acids in a sample. Preferably, a combination comprising one or more polynucleotide molecules selected from SEQ ID NOs:1-1558, more preferably selected from SEQ ID NOs:1-396, more preferably selected from SEQ ID NOs:1-217, are used to prepare probes that are hybridized with nucleic acids of a test sample, forming hybridization complexes that are detected and compared with those of a standard, such that differences between the sample and standard hybridization complexes are indicative of differential expression of nucleic acids in the sample. In a preferred embodiment, nucleic acid probes are made to specifically detect transcripts or fragments thereof produced by one or more of the genes or gene fragments identified in Table 2. In certain preferred embodiments, the nucleic acids of the sample may be amplified prior to hybridization.

In another aspect of the invention, methods are provided for assaying OA-associated polypeptides in a sample. Preferably, polynucleotide sequences selected from SEQ ID NOs:1-1558, more preferably selected from SEQ ID NOs:1-396, more preferably selected from SEQ ID NOs:1-217 are used to prepare protein-binding probes that specifically bind to translation products of those polypeptides or fragments thereof. These probes are reacted with a test sample, forming binding complexes that are detected and compared with those of a standard, such that differences between the sample and standard binding complexes are indicative of differential expression of polypeptides in the sample. In a preferred embodiment, protein-binding probes are made to specifically detect polypeptides or fragments thereof produced by one or more of the genes or gene fragments identified in Table 2.

According to certain preferred embodiments of the invention, the assays described herein for the detection of OA-associated transcription and translation products may be used in methods useful for determining a diagnosis and/or prognosis for osteoarthritis in a patient. According to an embodiment of the invention, a typical diagnostic test will comprise obtaining a sample of cells or tissue from a patient in which OA-associated gene expression is expected to occur. Such cells or tissues include, but are not limited to, cartilage tissue and chondrocytes. The sample is then analyzed for either 1) increased or decreased expression of one or more selected genes, via detection of mRNA or protein, or 2) a particular gene expression profile, for example, via gene or protein array technology, as described herein. Such a diagnostic procedure should lead to a determination of whether indications of osteoarthritis are present in the patient.

In another embodiment of the invention, the diagnostic procedures described herein may also be extended to provide prognostic information regarding a patient's recovery from OA, or to monitor a patient's progress in response to a therapeutic regimen. In these situations, the diagnostic assay is performed at intervals during the patient's recovery or course of treatment, and a change in expression of a target gene, or a particular change in the pattern of gene expression, is indicative of the patient's level of recovery or improvement.

In one aspect of the invention, assays are provided for identifying substances effective in treatment modalities for osteoarthritis. In one embodiment of the invention, a method is provided for measuring the effect of a test substance on the expression profile of genes differentially expressed in osteoarthritis, comprising the steps of: a) obtaining a standard expression profile from a first sample by measuring transcription or translation products of two or more genes corresponding to two or more genes or gene fragments identified in Tables 1 and/or 2 in the absence of the test substance; b) obtaining a test expression profile from a second sample by measuring the transcription or translation products of two or genes or gene fragments identified in Tables 1 and/or 2 expressed in the presence of the test substance; c) comparing the standard expression profile the test expression profile, wherein a change in the test expression profile compared to the standard expression profile is indicative of an effect of the test substance on the expression profile of genes differentially expressed in osteoarthritis compared to a non-osteoarthritic condition. Preferably, the two or more genes or gene fragments correspond to two or more of the genes or gene fragments identified in Table 3 (SEQ ID NOs:1-396). More preferably, the two or more genes or gene fragments correspond to two or more of the genes or gene fragments identified in Table 4 (SEQ ID NOs:1-217). In certain preferred embodiments, the samples are obtained from cultured cells. In this case, the standard expression profile is obtained from cells that have not been contacted with the test substance, while the test expression profile is obtained from cells that have been contacted with a test substance.

Test compounds may include proteins, polypeptides, nucleic acids, small molecule pharmaceuticals, vitamins, minerals, fatty acids, polysaccharides, extracts, nutriceuticals, and the like. In a preferred embodiment, the test compounds are nutrients that may be added to food or other dietary substances, or that may be taken as a dietary supplement. As exemplified herein, such nutrients include, but are not limited to, fatty acids such as omega-3 fatty acids (e.g., eicosapentaenoic acid) and omega-6 fatty acids (e.g., arachidonic acid), glucosamine, chondroitin sulfate and vitamin D derivatives such as 1α,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3.

One type of assay according to an embodiment of the invention involves measuring the activity of the protein encoded by one of the aforementioned OA-associated genes in the presence or absence of a candidate substance. Such activity assays are well known in the art. If a cell-free activity assay is available for the selected protein, such an assay is simply conducted on the purified protein in the presence or absence of the test substance. Candidate substances are selected based on their ability to positively or negatively regulate activity of the purified protein. It should be noted that assays of this type may be performed, for example, in a recombinant cellular system, as described below. They can also be performed, for example, in a cell-free system in some instances.

For such in vitro activity assays, it is desirable to have a source of the purified protein of interest. One or more of the protein products of the genes mentioned above may be commercially available, or purifiable in significant quantities from an appropriate biological source, e.g., cultured cells. Alternatively, the proteins may be recombinantly produced from an isolated gene or cDNA by expression in a suitable procaryotic or eucaryotic expression system, and thereafter purified, as is also well known in the art.

Another embodiment of the invention comprises in vitro cellular assays for expression of OA-associated genes or activity of their encoded proteins. For these embodiments, a nucleic acid construct comprising an OA-associated gene according to an aspect of the invention is introduced into host cells. In a preferred embodiment, mammalian cell lines are utilized. Host cells contemplated for use include, but are not limited, to NIH3T3, CHO, HELA, and COS, as well as non-mammalian cells such as yeast, bacteria and insect cells. The coding sequences are operably linked to appropriate regulatory expression elements suitable for the particular host cell to be utilized. Methods for introducing nucleic acids into host cells are well known in the art. Such methods include, but are not limited to, transfection, transformation, calcium phosphate precipitation, electroporation and lipofection. The recombinant cells may be used to identify compounds which modulate expression of the OA-associated genes or activity of their encoded proteins.

For gene expression assays, it is preferred to prepare an artificial construct comprising the promoter of a selected OA-associated gene, operably linked to a reporter gene. The reporter construct may be introduced a cultured cell, including, without limitation, the standard host cell lines described above, or other suitable cells, for example, cartilage-related cells such as chondrocytes. The assay is performed by monitoring expression of the reporter gene in the presence or absence of a test compound. Candidate substances are selected based on their ability to positively or negatively affect expression of the gene.

In another embodiment of the invention, OA-associated genes and gene fragments described herein may be used to manipulate the genome of non-human animal subjects. Methods of manipulating the genomes of a variety of animals are known to those of skill in the art. Such methods may include, without limitation, the production of transgenic and gene-knockout animals. In a preferred embodiment of the invention, a gene or gene fragment identified in Table 2 is used to prepare a construct that is used to disrupt or “knock out” the corresponding endogenous gene in an animal, thus producing an animal having a null mutation for that gene locus. In some embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:1-1558. In some embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NO:1-396. In some embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NO:1-217. In other embodiments, the animals exhibit a reduction or complete elimination of the expression of one or more genes shown in Table 6. The transgenic animals are preferably mammals. In some embodiments, the transgenic animals are rodents (e.g., mice and rats). In other embodiments, the animals are, for example, goats, cats, dogs, cows, pigs, sheep, horses, non-human primates, rabbits, and guinea pigs. In some embodiments, small interfering RNAs are used to functionally disrupt the genes. Briefly, gene expression is inhibited by a short interfering RNA (siRNA) through RNA interference (RNAi) or post-transcriptional gene silencing (PTGS) (see, for example, Ketting et al. (2001)Genes Develop. 15:2654-2659). siRNA molecules can target homologous mRNA molecules for destruction by cleaving the mRNA molecule within the region spanned by the siRNA molecule. Accordingly, siRNAs capable of targeting and cleaving mRNA of the gene products shown in Table 6 may be used to decrease or eliminate expression of one or more of these genes. In other embodiments, siRNAs capable of targeting and cleaving mRNA of one or more of the genes shown in Table 1 (SEQ ID NOS:1-1558) may be used to decrease or eliminate expression of one or more of these genes.

In another embodiment of the invention, OA-associated genes and gene fragments described herein are used to design molecules that may be used to interfere with the expression of one or more OA-associated genes; such molecules may include, without limitation, RNA interference probes and antisense molecules.

Another aspect of the invention features compositions of matter to facilitate practice of the assays described above. These compositions may comprise collections of two or more probes or primers for use in detecting differentially expressed OA-related genes, gene fragments and encoded proteins according to certain aspects of the invention. In one embodiment, the compositions may comprise collections of two or more oligonucleotides or polynucleotides that specifically hybridize with nucleic acid molecules selected from SEQ ID NOS:1-1558. Preferably, the compositions may comprise collections of two or more oligonucleotides or polynucleotides that specifically hybridize with nucleic acid molecules selected from SEQ ID NOS:1-396. More preferably, the compositions may comprise collections of two or more oligonucleotides or polynucleotides that specifically hybridize with nucleic acid molecules selected from SEQ ID NOS:1-217. Preferably, the composition may comprise collections of two or more oligonucleotides or polynucleotides that specifically hybridize with genes and/or gene fragments selected from the genes and gene fragments identified in Table 2. The collection may comprise a primer pair for amplifying the sequence. In certain preferred embodiments, amplification may be performed using Polymerase Chain Reaction (PCR), more preferably quantitative PCR (qPCR). In a preferred embodiment, the collection comprises a larger plurality of probes, e.g., about 10, 50, 200, 400, 1000 or more probes, each of which hybridizes specifically with part or all of one of the sequences of SEQ ID NOS:1-1558. In a preferred embodiment, nucleic acid probes are immobilized on a solid support. In a particularly preferred embodiment, they are immobilized in an array format, most preferably in a miniature or micro-array. Such micro-arrays are known in the art, and are sometimes referred to as “DNA chips,” “microchips,” “biological chips” and other similar terms, and may contain the entire array of genes or gene fragments altered by OA, in addition to those represented in Tables 1 and 2.

In another embodiment, these compositions comprise two or more protein binding substances capable of specifically binding proteins or protein fragments encoded by the genes and gene fragments identified in Tables 1 and 2. In a preferred embodiment the binding substances are antibodies and the collection comprises two or more antibodies for detecting two or more proteins or peptides encoded by SEQ ID NOS:1-1558, respectively. Preferably, these compositions comprise two or more protein binding substances capable of specifically binding proteins or protein fragments encoded by the genes and gene fragments of SEQ ID NOS:1-396. More preferably, these compositions comprise two or more protein binding substances capable of specifically binding proteins or protein fragments encoded by the genes and gene fragments of SEQ ID NOS:1-217. Such binding substances may be any molecule to which the protein or peptide specifically binds, including DNA (for DNA binding proteins), antibodies, cell membrane receptors, peptides, cofactors, lectins, sugars, polysaccharides, cells, cell membranes, organelles and organellar membranes. In a preferred embodiment, the collection comprises a larger plurality of antibodies, e.g., about 10, 50, 200, 400, 1000 or more, each of which binds immunospecifically with part or all of a protein or peptide encoded by genes or gene fragments identified in Tables 1 and/or 2. In a preferred embodiment, the antibodies are immobilized on a solid support. In a particularly preferred embodiment, they are immobilized in an array format, most preferably in a miniature or micro-array, as described above for oligonucleotide probes, and may contain the entire array of proteins altered by OA, in addition to genes or gene fragments identified in Tables 1 and 2.

Another embodiment of the present invention relates to substances or compounds identified in any of the methods described herein as having an effect on the expression profile of genes differentially expressed in OA. Preferably, such substances will be effective in the treatment and/or prevention of OA.

Still another aspect of the invention features test kits for use in one or more of the assays described herein. One type of kit comprises one or more pairs of primers for amplifying nucleic acids corresponding to the OA-associated genes and gene fragments described herein. The kit may further comprise samples of total mRNA derived from tissue of various physiological states, for use as controls. The kit may also comprise buffers, nucleotide bases, and other compositions to be used in hybridization and/or amplification reactions. Each solution or composition may be contained in a vial or bottle and all vials held in close confinement in a box for commercial sale.

Another type of kit comprises one or more nucleic acid or protein-binding probes, wherein the nucleic acid probe hybridizes specifically with a OA-associated gene or gene fragment according to certain aspects of the invention, or the protein-binding probe specifically binds to a protein encoded by the OA-associated gene or gene fragment. Preferably, the protein-binding probe is an antibody that is immunologically specific for the protein encoded by the OA-associated gene or gene fragment. In preferred embodiments, the nucleic acid or protein-binding probes are immobilized on a solid support. In a particularly preferred embodiment, the kit comprises immobilized arrays of nucleic acid or protein-binding probes, the arrays comprising probes specific for a plurality of the OA-associated genes or gene fragments described herein, or proteins encoded thereby. These kits also may contain appropriate control samples of mRNA or protein from tissues of known physiological state, to be used as controls in the assays. They may further comprise buffers and reagents for performing the assays. Each solution, reagent or composition in the kit may be contained in a vial or bottle and all vials held in close confinement in a box for commercial sale. Preferably, kits may further comprise instructions for performing an assay of gene expression.

In another aspect, the invention provides a method for altering biological profile of cells through inducing a change in the gene expression profile of the cells with respect to genes involved in OA. The method involves administering to cells an effective amount of a compound that alters the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:1-1558. In some embodiments, the compound affects the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:1-396. In some embodiments, the compound affects the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:1-217. In other embodiments, the compound affects the expression of one or more genes having the gene products shown in Table 6. The invention also provides a method of affecting the expression of genes involved in OA comprising exposing cells to an effective amount of a compound that modulates expression of one or more genes having a sequence selected from SEQ ID NOs:1-1558. In some embodiments, the compound affects the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:1-396. In some embodiments, the compound affects the expression of one or more genes having a nucleic acid sequence selected from SEQ ID NOs:1-217. In other embodiments, the compound affects the expression of one or more genes having the gene products shown in Table 6.

In some embodiments the cells are cells associated with symptoms of osteoarthritis. In some embodiments the cells are chondrocytes. In some embodiments the compounds are administered to cells in vitro. In other embodiments the compounds are administered to cells in vivo. The compounds may be administered to subjects via any route of administration. Preferably, the subjects are vertebrates. More preferably, the subjects are mammals including dogs, cats and humans.

The change in gene expression is preferably at least a 1.01 fold difference. More preferably, it is at least a 1.05, 1.10, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.0, 3.25, 3.50, 3.75, 4.0 fold difference or more.

Chondroitin sulfate was shown to have an effect on a wide variety of OA-associated genes as shown in detail in Tables 7-12. Glucosamine was also found to have an effect on a variety of OA-associated genes as shown in detail in Tables 13-18. 1α,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 also affected the expression of OA-related genes as shown in Tables 19-20. Eicosapentaenoic acid (EPA) and arachidonic acid (AA) were also shown to affect OA-related genes as shown in Tables 21-23.

The following examples are provided to describe the invention in greater detail. They are intended to illustrate, not to limit, the invention.

EXAMPLE 1 Extraction of RNA from Chondrocytes

Normal and osteoarthritic canine cartilage chondrocytes (N₂-flash frozen) were obtained and stored at −80° C. Osteoarthritic chondrocytes originated from canines clinically diagnosed with osteoarthritis undergoing total hip replacement. 300 to 500 mg were ground in N₂ (mortar and pestle) and transferred to a clean, pre-chilled, 50 ml tube. Trizol (2 ml/100 mg) was added and the mixture was homogenized using a Polytron for 2×30 seconds, and 1 minute (high speed). The homogenate was then centrifuged at 10,000×g for 10 minutes at 4° C. The supernatant was removed and 0.2 volumes chloroform added to the supernatant, vortexed, and centrifuged at 10,000×g for 15 minutes at 4° C. The upper aqueous phase was removed and 5 volumes of 4 M Guanidine thiocyanate, 25 mM sodium citrate, 0.5% sarkosyl, 0.1 M beta-mercaptoethanol and 0.475 volumes of 100% ethanol were added to the upper aqueous phase. The solution was then applied to Qiagen RNAqueous mini-columns (cat #74104), using a vacuum manifold (according to the manufacture's directions) for further purification of the RNA. The purified RNA was then ethanol precipitated to concentrate, resuspended in DEPC water and DNAse I treated to remove residual DNA. The DNA-free™ DNAse Treatment kit from Ambion (cat #1906) was used for DNAse I treatment according to the manufacture's directions.

RNA was quantitated in a Beckman DU 640B spectrophotometer at 260 nm (Beckman Coulter, Inc., 4300 N. Harbor Boulevard, P.O. Box 3100, Fullerton, Calif. 92834-3100). Absorbance of 1 at 260 nm is equivalent to 40 μg RNA/ml. Typical yields were 0.65 to 0.8 μg/μl. Quality of RNA was determined by the absorbance at 260 nm/280 nm with a typical ratio of 1.7-2.0. Quality was also assessed by electrophoresis in a 1% agarose gel/formaldehyde/Tris-borate-EDTA (TBE), pH 7.8 buffer (90 mM Tris, 90 mM boric acid, 2 mM EDTA). Approximately 1 to 3.5 μg RNA was loaded (2 to 5 μl) after being mixed with 15 μl gel loading solution (10 mM Tris pH 7.5, 1 mM EDTA, 0.02% bromophenol blue, 10% glycerol). The gel was run at 50 Volts for 3-4 hours, stained with SYBR Green I (Molecular Probes, Inc., PO Box 22010, Eugene, Oreg. 97402-0469, 4849 Pitchford Ave., Eugene, Oreg. 97402-9165) at a dilution of 1:10,000 for 30 minutes in the dark and scanned using a Hitachi FMBIO II Fluorescent scanner at 505 nm (Hitachi Genetic Systems, 1201 Harbor Bay Parkway Step. 150, Alameda, Calif. 94502).

EXAMPLE 2 Differential Display

Fluorescent differential display was performed using one of three anchored primers in combination with one of 80 arbitrary primers (GenHunter). In all, 240 PCR reactions were carried out. Reactions were separated using PAGE and visualized using a fluorescent scanner (FMBIOII, Hitachi). Bands representing differentially expressed genes were excised, reamplified and run on an agarose gel to verify size. These were subsequently subcloned (PCR-TRAP, GenHunter) and sequenced.

Differential display was performed using GenHunter's RNAimage® kit or RNAspectra™ green fluorescent mRNA differential display systems (GenHunter Corporation, 624 Grassmere Park Drive, Suite 17, Nashville, Tenn. 37211). Approximately 200 ng of RNA was reverse transcribed in the following reaction (final concentration): RT buffer (25 mM Tris-Cl, pH 8.3, 37.6 mM KCl, 1.5 mM MgCl₂, 5 mM DTT), 625 μM ea. dNTP, 50 pmol H-T₁₁G primer (GenHunter) (5′AAGCTTTTTTTTTTTG 3′) (SEQ ID NO:1559), or H-T₁₁C primer (GenHunter) (5′AAGCTTTTTTTTTTTC 3′) (SEQ ID NO:1560), or H-T₁₁A primer (GenHunter) (5′AAGCTTTTTTTTTTTA 3′) (SEQ ID NO:1561), in a total volume of 19 μl. 1 μl (100 units/μl) of MMLV reverse transcriptase was added ten minutes into the 37° C. step in a thermocycler (GeneAmp PCR System 9700, PE Applied Biosystems, 850 Lincoln Center Dr., Foster Calif. 94404) and the following reaction performed: 65° C. 5 minutes, 37° C. 60 minutes, 75° C. 5 minutes followed by a hold at 4° C. Two μl of the reverse transcription reaction was used in the following polymerase chain reaction: PCR buffer (10 mM Tris-Cl, pH 8.4, 50 mM KCl, 1.5 mM MgCl₂, 0.001% gelatin), 50 μM each dNTP, 5 pmol Fluorescein-labeled H-T₁₁G primer (GenHunter) (Fluorescein-labeled primer, 5′ AAGCTTTTTTTTTTTG 3′) (SEQ ID NO:1562), or Fluorescein-labeled H-T₁₁C primer (GenHunter) (Fluorescein-labeled primer, 5′ AAGCTTTTTTTTTTTC 3′) (SEQ ID NO:1563) or Fluorescein-labeled H-T₁₁A primer (GenHunter) (Fluorescein-labeled primer, 5′ AAGCTTTTTTTTTTTA 3′) (SEQ ID NO:1564) one of the H-AP primers provided in the kit at 200 pM, 1 unit of Amplitaq DNA polymerase (PE Applied Biosystems, 850 Lincoln Center Dr., Foster Calif. 94404) in a total of 20 μl.

The following thermocycler reaction was used: 40 cycles of 94° C. 15 seconds, 40° C. 2 minutes, 72° C. 30 seconds, followed by 72° C. 5 minutes and a 4° C. hold.

5 μl of each PCR sample was mixed with 5 μl blue dextran loading buffer and 10 μl deionized formamide and electrophoresed on a 6% polyacrylamide gel at 55 watts for 3 hours in TBE buffer. The gel was scanned using a Hitachi FMBIO II at 505 nm. cDNA bands differentially expressed were excised with a razor, placed in a 1.5 ml tube, soaked in 100 μl sterile water for 10 minutes and then boiled for 15 minutes. Tubes were centrifuged for 2 minutes at 10,000×g and the supernatant transferred to a new tube. 10 μl 3M sodium acetate, 5 μl glycogen (10 mg/ml) and 450 μl 100% ethanol was added to the supernatant and the tubes were placed at −80° C. overnight. Samples were centrifuged at 10,000×g for 10 minutes at 4° C. and the supernatant was removed. cDNA pellets were washed with cold (−20° C.) 85% ethanol, spun as above for 1 minute and the supernatant was removed. cDNA pellets were resuspended in 10 μl sterile water.

Four μl samples of the cDNA extracts were amplified the same as in the above PCR reaction with the following exceptions: 40 μl total reaction volume; 20 μM ea. dNTP; 200 pM unlabeled primer H-T₁₁G, H-T₁₁C, or H-T₁₁A (GenHunter) and 2 units of Amplitaq DNA polymerase (PE Applied Biosystems). PCR conditions were the same as above. 15 μl of the amplified cDNA extracts were mixed with 3 μl 6× loading dye (0.25% bromophenol blue, 0.25% xylene cyanol FF, 30% glycerol) and electrophoresed in a 1.5% agarose gel. The gel was run at 100 volts for 2 to 3 hours in TBE buffer, stained/visualized the same as above. Bands were excised with a razor and cDNA extracted according to Qiagen's QIAEX® II Gel Extraction Kit (Qiagen, Inc., 28159 Avenue Stanford, Valencia, Calif. 91355). Three hundred μl QX1 buffer and 10 μl QIAEX® II suspension was added to each gel slice in a 1.5 ml tube and incubated at 50° C. for 10 minutes. Tubes were vortexed every 2 minutes during incubation. Tubes were centrifuged 10,000×g for 30 seconds and the supernatant was discarded. Pellets were washed once with 500 μl Buffer QX1 and twice with buffer PE (vortexing and centrifuging as above for each wash). Pellet was air dried for 10 minutes and 20 μl sterile water was added. Tubes were incubated for 5 minutes at room temperature and cDNA was eluted by centrifugation as above for 30 seconds. Supernatant was then transferred to a new 1.5 ml tube and stored at −20° C.

Amplified gel purified cDNA was subcloned according to GenHunter's PCR-TRAP® Cloning System Kit (GenHunter Corporation, 624 Grassmere Park Drive, Suite 17, Nashville, Tenn. 37211). 5 μl amplified gel purified cDNA was added to 300 ng PCR-TRAP® vector, ligase buffer (50 mM Tris-Cl, pH 7.8, 10 mM MgCl₂, 10 mM DTT, 10 mM ATP, 5 μg BSA) and 200 units T4 DNA ligase, mixed, and incubated overnight at 16° C. GH competent cells (E. coli del(lac-pro) ara thi (φ80dlacZdelM15)) were transformed with ligation reaction by mixing 10 μl ligation reaction to 100 μl GH competent cells on ice in 1.5 ml tubes. Tubes were incubated on ice for 45 minutes, heat shocked at 42° C. for 2 minutes and then incubated on ice for 2 minutes. 400 μI LB broth (Luria-Bertani, Difco) was added to each tube and the tubes were incubated at 37° C. for 1 hour with shaking (250 rpm). 200 μl of these transformations were plated onto LB-agar-tet plates (LB-agar, Difco, tetracycline 20 μg/ml) and incubated overnight at 37° C.

Colonies were checked for insert using GenHunter's colony lysate PCR protocol. Colonies were picked with a clean pipette tip and placed in 50 μl colony lysate buffer (GenHunter, TE with 0.1% Tween 20) in a microfuge tube. Tubes were boiled for 10 minutes, centrifuged at 10,000×g for 2 minutes and the corresponding lysate (supernatant) was transferred to a new microfuge tube. 2.0 μl of lysate was added to PCR buffer, 20 μM ea. dNTP, 200 (pmol ea. of Lgh (5′CGACAACACCGATAATC) (SEQ ID NO:1565) and Rgh (5′ GACGCGAACGAAGCAAC) (SEQ ID NO:1566) primers and 1 unit of Amplitaq DNA polymerase (PE Applied Biosystems) in a total volume of 20 μl. The following thermocycler reaction was used: 30 cycles of 94° C. for 30 seconds, 52° C. for 40 seconds and 72° C. for 1 minute followed by 72° C. for 5 minutes and a 4° C. hold. PCR products were analyzed in a 1.5% agarose gel the same as above.

3-5 ml LB broth was inoculated with appropriate colonies and incubated overnight at 37° C. at 250 rpm. Plasmids were isolated according to Qiagen's QIAprep Plasmid protocol. Bacteria were pelleted (10,000×g, 30 seconds) using 2×1.5 ml inoculated broth and the supernatant was removed. Pelleted bacteria were resuspended in 250 μl buffer P1, 250 μl buffer P2 was then added and tubes were mixed by gentle inversion. 350 μl buffer N3 was added, tubes were mixed by gentle inversion and then centrifuged for 10 minutes. Supernatants were added to a QIAprep column and centrifuged for 30 seconds. Flow-throughs were discarded, 0.5 ml of buffer PB was added to column and tubes were centrifuged for 30 seconds. Columns were washed with 0.75 ml buffer PE and centrifuged for 30 seconds. Flow-throughs were discarded and tubes were spun an additional minute. DNA was eluted from the column by adding 50 μl sterile water to the column. The column was incubated at room temperature for 1 minute and then centrifuged for 1 minute. Resulting supernatant containing plasmid DNA was quantitated as above (absorbance of 1 at 260 nm equals 50 μg/ml) with a typical yield of 350 μg/ml and a 260 nm/280 nm ratio of 1.8.

Sequencing reactions used 200 to 500 ng plasmid DNA in the ABI Prism BigDye Terminator Cycle Sequencing Ready Reaction Kit (PE Applied Biosystems, 850 Lincoln Center Dr., Foster Calif. 94404). 0.8 μl of primer (0.16 μm final concentration of either Lgh or Rgh, GenHunter) was added to plasmid DNA along with 4.0 μl Teminator Reaction Mix (containing AmpliTaq DNA Polymerase, FS, deoxynucleoside triphosphates, MgCl₂, Tris-HCL buffer, pH 9.0, A-Dye Terminator labeled with dichloro(R6G), C-Dye Terminator labeled with dichloro(ROX), G-Dye Terminator labeled with dichloro(R110) and T-Dye Terminator labeled with dichloro(TAMRA)) and brought to a final volume of 10 μl with sterile water. The following thermocycler reaction was used: 25 cycles of 96° C. for 10 seconds, 50° C. for 5 seconds, 60° C. for 4 minutes followed by a 4° C. hold.

Unincorporated dye-terminators were removed from the sequencing reactions according to Qiagen's DyeEx spin protocol. Prepared DyeEx spin columns were placed in 2.0 ml microfuge tubes and centrifuged at 750×g for 3 minutes. Columns were placed in new tubes, sequencing reactions were added to columns and centrifuged, as above, for 3 minutes. The eluate was placed at 74° C. until dry.

5 μl of formamide/blue dextran (5:1 ratio) was added to each dried sequencing pellets. 1.5 μl to 2.0 μl was then added to a 5% polyacrylamide gel (in TBE buffer) on a Perkin Elmer ABI Prism 377 automated DNA sequencer.

Each isolated plasmid clone was sequenced 2-6 times (2-6 different sequencing reactions, 1-3 times for each primer, Lgh or Rgh). Sequence files from the ABI 377 sequencer were transferred to Genetic Computer Group's Wisconsin Package and a corresponding consensus sequence was determined.

Approximately 1750 clones were isolated using differential display. All genes that appeared to be differentially expressed were selected. A representational polyacrylamide gel image is shown in FIG. 1. Panel A represents the gel prior to band excision and panel B represents the same gel after band excision. Sizes of clones ranged from 90 b.p. to 1150 b.p., with an average size of 300 b.p. After filtering the sequences for redundant sequences, dimers, E. coli fragments, fragments <100 b.p. etc., 1558 remained. Sequences obtained (SEQ ID NOs:1-1558) are shown in Table 1, which is appended herewith and which forms part of the present specification.

The sequences obtained were BLASTed against the human, mouse and dog public domain genomes to get a first hit. To be considered a hit at this stage, the match had to cover more than 50% of the sequence and an Expect value (E value) of less than 0.002. The first hits were used to extend the sequence using the respective genome. The sequences were either extended 2 kb to the 5′ or 3′ side of the hit. The extended sequences were then used to BLAST against public domain protein databases (Ensembl, swissprot/trembl). The respective hits (those with an Expect value of less than 0.002, in this case) were consolidated and used for the annotations. In some cases, this strategy did not give hits, and in these situations the original sequences were BLASTed directly against swissprot/trembl or Ensembl proteins. In this case, hits were considered when the Expect value was less than 0.002.

Results of BLAST analysis (as of Jan. 28, 2004) of sequences isolated by differential display are shown in Table 2, which is appended herewith and which forms part of the present specification. The sequences are listed in the leftmost column by the gene ID designations (clone numbers) employed by the inventors herein. Many sequences matched with a Description of a previously-identified gene; the Description column also includes the source database and the corresponding database accession number. Table 2 includes additional information from a number of databases, including Ensemble Gene IDs, Ensemble Transcript IDs, Swissprot/Ensemble, OMIM (Online Mendelian Inheritance in Man), RefSeq, Pfam, InterPro and HUGO. Information is also shown regarding Chromosome Number (#) and Chromosome Location for many of the sequences. Additionally, the column labeled “Signal peptide” indicates the sequences for which a predicted signal peptide occurs in the amino acid sequence; the column labeled “TMHMM” (Transmembrane Hidden Markov Model) indicates sequences for which a predicted transmembrane region occurs in a protein sequence.

Table 6 lists clones demonstrating homology to previously-identified genes.

TABLE 6 CaMax Gene ID Description SEQ ID NO CaMax: BUTYRATE RESPONSE FACTOR 2 (TIS11D PROTEIN) (EGF- 1360 1006b RESPONSE FACTOR 2) (ERF-2). [Source: SWISSPROT; Acc: P47974] CaMax: BUTYRATE RESPONSE FACTOR 2 (TIS11D PROTEIN) (EGF- 1361 1007a RESPONSE FACTOR 2) (ERF-2). [Source: SWISSPROT; Acc: P47974] CaMax: GRAVE'S DISEASE CARRIER PROTEIN (GDC) (GRAVE'S DISEASE 905 1009c AUTOANTIGEN) (GDA) (MITOCHONDRIAL SOLUTE CARRIER PROTEIN HOMOLOG). [Source: SWISSPROT; Acc: P16260] CaMax: ZINC FINGER PROTEIN 333. [Source: SWISSPROT; Acc: Q96JL9] 934 1019a CaMax: CALCITONIN GENE-RELATED PEPTIDE TYPE 1 RECEPTOR 935 1020a PRECURSOR (CGRP TYPE 1 RECEPTOR). [Source: SWISSPROT; Acc: Q16602] CaMax: TIGGER TRANSPOSABLE ELEMENT DERIVED 1; JERKY (MOUSE) 938 1029a HOMOLOG-LIKE. [Source: RefSeq; Acc: NM_145702] CaMax: POLY [ADP-RIBOSE] POLYMERASE-3 (EC 2.4.2.30) (PARP-3) 1363 1044c (NAD(+) ADP-RIBOSYLTRANSFERASE-3) (POLY[ADP-RIBOSE] SYNTHETASE-3) (PADPRT-3) (HPARP-3) (IRT1). [Source: SWISSPROT; Acc: Q9Y6F1] CaMax: HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN H (HNRNP 439 104a H). [Source: SWISSPROT; Acc: P31943] CaMax: LEUKEMIA-ASSOCIATED PROTEIN WITH A CXXC DOMAIN. 1160 1061a [Source: SPTREMBL; Acc: Q8NFU7] CaMax: FERRITIN HEAVY CHAIN (FERRITIN H SUBUNIT). 440 106a [Source: SWISSPROT; Acc: P02794] CaMax: RAS-RELATED PROTEIN RAB-14. [Source: SWISSPROT; Acc: P35287] 1320 1105a CaMax: STAR-RELATED LIPID TRANSFER PROTEIN 13 (STARD13) (START 1262 1108a DOMAIN-CONTAINING PROTEIN 13) (46H23.2). [Source: SWISSPROT; Acc: Q9Y3M8] CaMax: SESTRIN 1 (P53-REGULATED PROTEIN PA26). 898 1111b [Source: SWISSPROT; Acc: Q9Y6P5] CaMax: GOLGI PHOSPHOPROTEIN 3; GOLGI PROTEIN; GOLGI 1366 1120a PERIPHERAL MEMBRANE PROTEIN 1, 34 KDA; GOLGI- ASSOCIATED PROTEIN; COAT-PROTEIN. [Source: RefSeq; Acc: NM_022130] CaMax: MYOCYTE-SPECIFIC ENHANCER FACTOR 2C. 1172 1134a [Source: SWISSPROT; Acc: Q06413] CaMax: FORKHEAD BOX PROTEIN P2 (CAG REPEAT PROTEIN 44) 1173 1135a (TRINUCLEOTIDE REPEAT-CONTAINING GENE 10 PROTEIN). [Source: SWISSPROT; Acc: O15409] CaMax: COLLAGEN ALPHA 1(XV) CHAIN PRECURSOR. 1436 1145a [Source: SWISSPROT; Acc: P39059] CaMax: HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN H (HNRNP 439 104a H). [Source: SWISSPROT; Acc: P31943] CaMax: TROPOMYOSIN 1 ALPHA CHAIN (ALPHA-TROPOMYOSIN). 1322 1169b [Source: SWISSPROT; Acc: P09493] CaMax: DYNEIN HEAVY CHAIN, CYTOSOLIC (DYHC) (CYTOPLASMIC 943 1177c DYNEIN HEAVY CHAIN 1) (DHC1) (FRAGMENT). [Source: SWISSPROT; Acc: Q14204] CaMax: T-LYMPHOMA INVASION AND METASTASIS INDUCING PROTEIN 885 1184a 1 (TIAM1 PROTEIN). [Source: SWISSPROT; Acc: Q13009] CaMax: VAV-3 PROTEIN. [Source: SWISSPROT; Acc: Q9UKW4] 1324 1213d CaMax: WD-REPEAT PROTEIN 3. [Source: SWISSPROT; Acc: Q9UNX4] 908 1243a CaMax: PROPIONYL-COA CARBOXYLASE ALPHA CHAIN, 874 1267a MITOCHONDRIAL PRECURSOR (EC 6.4.1.3) (PCCASE ALPHA SUBUNIT) (PROPANOYL-COA: CARBON DIOXIDE LIGASE ALPHA SUBUNIT). [Source: SWISSPROT; Acc: P05165] CaMax: PROPIONYL-COA CARBOXYLASE ALPHA CHAIN, 874 1267a MITOCHONDRIAL PRECURSOR (EC 6.4.1.3) (PCCASE ALPHA SUBUNIT) (PROPANOYL-COA: CARBON DIOXIDE LIGASE ALPHA SUBUNIT). [Source: SWISSPROT; Acc: P05165] CaMax: PROTEIN TRANSPORT PROTEIN SEC24A (SEC24-RELATED 872 1272a PROTEIN A) (FRAGMENT). [Source: SWISSPROT; Acc: O95486] CaMax: IDN3 PROTEIN ISOFORM A. [Source: RefSeq; Acc: NM_133433] 952 1287c CaMax: IDN3 PROTEIN ISOFORM A. [Source: RefSeq; Acc: NM_133433] 63 1288a CaMax: HEAT SHOCK PROTEIN HSP 90-BETA (HSP 84) (TUMOR SPECIFIC 234 128a TRANSPLANTATION 84 KDA ANTIGEN) (TSTA). [Source: SWISSPROT; Acc: P11499] CaMax: ATP-DEPENDENT DNA HELICASE II, 80 KDA SUBUNIT (LUPUS KU 44 1292c AUTOANTIGEN PROTEIN P86) (KU86) (KU80) (86 KDA SUBUNIT OF KU ANTIGEN) (THYROID-LUPUS AUTOANTIGEN) (TLAA) (CTC BOX BINDING FACTOR 85 KDA SUBUNIT) (CTCBF) (CTC85) (NUCLEAR FACTOR IV) (DNA-REPAIR PROTEIN XRCC5). [Source: SWISSPROT; Acc: P13010] CaMax: BIFUNCTIONAL AMINOACYL-TRNA SYNTHETASE [INCLUDES: 1245 1294b GLUTAMYL-TRNA SYNTHETASE (EC 6.1.1.17) (GLUTAMATE-- TRNA LIGASE); PROLYL-TRNA SYNTHETASE (EC 6.1.1.15) (PROLINE--TRNA LIGASE)]. [Source: SWISSPROT; Acc: P07814] CaMax: WD REPEAT AND FYVE DOMAIN CONTAINING 3 ISOFORM 1. 316 1299c [Source: RefSeq; Acc: NM_014991] CaMax: AMISYN; SYNTAXIN BINDING PROTEIN 6. 1371 1304a [Source: RefSeq; Acc: NM_014178] CaMax: UDP-N-ACETYLGLUCOSAMINE--PEPTIDE N- 1372 1322c ACETYLGLUCOSAMINYLTRANSFERASE 110 KDA SUBUNIT (EC 2.4.1.—) (O-GLCNAC TRANSFERASE P110 SUBUNIT). [Source: SWISSPROT; Acc: P56558] CaMax: CYSTEINE KNOT SUPERFAMILY 1, BMP ANTAGONIST 1; 1269 1341a GREMLIN. [Source: RefSeq; Acc: NM_013372] CaMax: TIGGER TRANSPOSABLE ELEMENT DERIVED 1; JERKY (MOUSE) 370 1354a HOMOLOG-LIKE. [Source: RefSeq; Acc: NM_145702] CaMax: ALPHA-(1,6)-FUCOSYLTRANSFERASE (EC 2.4.1.68) 1189 1361a (GLYCOPROTEIN 6-ALPHA-L-FUCOSYLTRANSFERASE) (GDP- FUCOSE--GLYCOPROTEIN FUCOSYLTRANSFERASE) (GDP-L- FUC: N-ACETYL-BETA-D-GLUCOSAMINIDE ALPHA1,6- FUCOSYLTRANSFERASE) (ALPHA1-6FUCT) (FUCOSYLTRANSFERASE 8). [Source: SWISSPROT; Acc: Q9BYC5] CaMax: CONNECTIVE TISSUE GROWTH FACTOR-LIKE PROTEIN 209 1366a PRECURSOR (CTGF-L) (WNT1 INDUCIBLE SIGNALING PATHWAY PROTEIN 2) (WISP-2) (CONNECTIVE TISSUE GROWTH FACTOR- RELATED PROTEIN 58). [Source: SWISSPROT; Acc: O76076] CaMax: CATENIN (CADHERIN-ASSOCIATED PROTEIN), ALPHA-LIKE 1; 392 1371a ALPHA-CATULIN. [Source: RefSeq; Acc: NM_003798] CaMax: M-PHASE PHOSPHOPROTEIN 8 (FRAGMENT). 491 137b [Source: SWISSPROT; Acc: Q99549] CaMax: ECOTROPIC VIRAL INTEGRATION SITE 5; NEUROBLASTOMA 911 1383a STAGE 4S GENE. [Source: RefSeq; Acc: NM_005665] CaMax: ACYL-COA DESATURASE (EC 1.14.19.1) (STEAROYL-COA 1330 1384a DESATURASE) (FATTY ACID DESATURASE) (DELTA(9)- DESATURASE). [Source: SWISSPROT; Acc: O00767] CaMax: NUCLEAR RECEPTOR COACTIVATOR 7; ESTROGEN RECEPTOR 858 1397b ASSOCIATED PROTEIN 140 KDA. [Source: RefSeq; Acc: NM_181782] CaMax: PDZ DOMAIN CONTAINING GUANINE NUCLEOTIDE EXCHANGE 306 1401c FACTOR (GEF) 1; RA(RAS/RAP1A-ASSOCIATING)-GEF; PDZ DOMAIN CONTAINING GUANINE NUCLEOTIDE EXCHANGE FACTOR(GEF)1; RA(RAS/RAP1A-ASSOCIATING)-GEF; PDZ DOMAIN CONTAINING GUANINE NUCLEOTIDE EXCHANGE FACTOR(GEF)1. [Source: RefSeq; Acc: NM_014247] CaMax: BAG-FAMILY MOLECULAR CHAPERONE REGULATOR-5 (BAG-5). 853 1409b [Source: SWISSPROT; Acc: Q9UL15] CaMax: PROTEIN PHOSPHATASE 1, REGULATORY (INHIBITOR) SUBUNIT 1247 1411a 12A; MYOSIN PHOSPHATASE, TARGET SUBUNIT 1. [Source: RefSeq; Acc: NM_002480] CaMax: CELL CYCLE PROGRESSION 8 PROTEIN. 981 1420c [Source: RefSeq; Acc: NM_020739] CaMax: MUCOSA ASSOCIATED LYMPHOID TISSUE LYMPHOMA 1248 1421a TRANSLOCATION PROTEIN 1 (EC 3.4.22.—) (MALT-LYMPHOMA ASSOCIATED TRANSLOCATION) (PARACASPASE). [Source: SWISSPROT; Acc: Q9UDY8] CaMax: SPARC-LIKE PROTEIN 1 PRECURSOR (HIGH ENDOTHELIAL 145 143.2c VENULE PROTEIN) (HEVIN) (MAST 9). [Source: SWISSPROT; Acc: Q14515] CaMax: SPARC-LIKE PROTEIN 1 PRECURSOR (HIGH ENDOTHELIAL 145 143.2c VENULE PROTEIN) (HEVIN) (MAST 9). [Source: SWISSPROT; Acc: Q14515] CaMax: TESTICAN-3 PRECURSOR. [Source: SWISSPROT; Acc: Q9BQ16] 969 1448a CaMax: ZINC FINGER PROTEIN CLONE 647. 1270 1449a [Source: SWISSPROT; Acc: P15622] CaMax: CYTOKINE-LIKE PROTEIN C17 PRECURSOR. 1450 1450a [Source: SWISSPROT; Acc: Q9NRR1] CaMax: ACTIVATED RNA POLYMERASE II TRANSCRIPTIONAL 850 1459c COACTIVATOR P15 (PC4) (P14). [Source: SWISSPROT; Acc: P53999] CaMax: 60S RIBOSOMAL PROTEIN L10 (QM PROTEIN) (TUMOR 455 145b SUPPRESSOR QM) (LAMININ RECEPTOR HOMOLOG). [Source: SWISSPROT; Acc: P27635] CaMax: UPREGULATED DURING SKELETAL MUSCLE GROWTH 5. 847 1469a [Source: RefSeq; Acc: NM_023211] CaMax: UPREGULATED DURING SKELETAL MUSCLE GROWTH 5. 847 1469a [Source: RefSeq; Acc: NM_023211] CaMax: DNA-BINDING PROTEIN INHIBITOR ID-4. 846 1476a [Source: SWISSPROT; Acc: P47928] CaMax: BTG2 PROTEIN (NGF-INDUCIBLE ANTI-PROLIFERATIVE PROTEIN 276 1477a PC3). [Source: SWISSPROT; Acc: P78543] CaMax: HOMEOBOX PROTEIN HOX-A3 (HOX-1E). 23 1481c [Source: SWISSPROT; Acc: O43365] CaMax: HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEINS A2/B1 195 1488b (HNRNP A2/HNRNP B1). [Source: SWISSPROT; Acc: P22626] CaMax: NADP-DEPENDENT LEUKOTRIENE B4 12- 458 150a HYDROXYDEHYDROGENASE (EC 1.1.1.—). [Source: SWISSPROT; Acc: Q14914] CaMax: PROTEIN PHOSPHATASE METHYLESTERASE-1. 147 1521b [Source: RefSeq; Acc: NM_016147] CaMax: CYSTINE/GLUTAMATE TRANSPORTER (AMINO ACID 1199 1546b TRANSPORT SYSTEM XC-) (XCT) (CALCIUM CHANNEL BLOCKER RESISTANCE PROTEIN CCBR1). [Source: SWISSPROT; Acc: Q9UPY5] CaMax: BTB (POZ) DOMAIN CONTAINING 5. 223 1551a [Source: RefSeq; Acc: NM_017658] CaMax: TRANSMEMBRANE PROTEIN 4. [Source: RefSeq; Acc: NM_014255] 1464 1577a CaMax: UNC-51-LIKE KINASE 2. [Source: RefSeq; Acc: NM_014683] 119 1631d CaMax: UNC-51-LIKE KINASE 2. [Source: RefSeq; Acc: NM_014683] 1550 1635a CaMax: UNC-51-LIKE KINASE 2. [Source: RefSeq; Acc: NM_014683] 1550 1635a CaMax: MACROPHAGE INFLAMMATORY PROTEIN-2-BETA PRECURSOR 465 164c (MIP2-BETA) (CXCL3) (GROWTH REGULATED PROTEIN GAMMA) (GRO-GAMMA). [Source: SWISSPROT; Acc: P19876] CaMax: CYTOCHROME C OXIDASE SUBUNIT IV ISOFORM 1, 1379 1690a MITOCHONDRIAL PRECURSOR (EC 1.9.3.1) (COX IV-1) (CYTOCHROME C OXIDASE POLYPEPTIDE IV). [Source: SWISSPROT; Acc: P10888] CaMax: CYTOCHROME C OXIDASE SUBUNIT IV ISOFORM 1, 1380 1692a MITOCHONDRIAL PRECURSOR (EC 1.9.3.1) (COX IV-1) (CYTOCHROME C OXIDASE POLYPEPTIDE IV). [Source: SWISSPROT; Acc: P10888] CaMax: FIBROBLAST GROWTH FACTOR RECEPTOR 2 PRECURSOR (EC 1333 1693b 2.7.1.112) (FGFR-2) (KERATINOCYTE GROWTH FACTOR RECEPTOR 2). [Source: SWISSPROT; Acc: P21802] CaMax: CASPASE RECRUITMENT DOMAIN PROTEIN 6. 1132 1705a [Source: SWISSPROT; Acc: Q9BX69] CaMax: T-CELL ACTIVATION PROTEIN. [Source: RefSeq; Acc: NM_033296] 1060 1717a CaMax: LEUKOCYTE ELASTASE INHIBITOR (LEI) 1064 1721a (MONOCYTE/NEUTROPHIL ELASTASE INHIBITOR) (M/NEI) (EI). [Source: SWISSPROT; Acc: P30740] CaMax: GOLGI AUTOANTIGEN, GOLGIN SUBFAMILY A MEMBER 4 1065 1722a (TRANS-GOLGI P230) (256 KDA GOLGIN) (GOLGIN-245) (72.1 PROTEIN). [Source: SWISSPROT; Acc: Q13439] CaMax: G-PROTEIN COUPLED RECEPTOR. [Source: RefSeq; Acc: NM_153832] 1066 1724a CaMax: EGF-LIKE MODULE-CONTAINING MUCIN-LIKE RECEPTOR 3 29 1727a ISOFORM A. [Source: RefSeq; Acc: NM_032571] CaMax: LEUCINE-RICH REPEAT-CONTAINING G PROTEIN-COUPLED 325 1744a RECEPTOR 4 PRECURSOR (G PROTEIN-COUPLED RECEPTOR 48). [Source: SWISSPROT; Acc: Q9BXB1] CaMax: TRANSCRIPTION INITIATION FACTOR IIF, BETA SUBUNIT (TFIIF- 243 174a BETA) (TRANSCRIPTION INITIATION FACTOR RAP30). [Source: SWISSPROT; Acc: P13984] CaMax: U1 SMALL NUCLEAR RIBONUCLEOPROTEIN 70 KDA (U1 SNRNP 340 1758a 70 KDA) (SNRNP70) (U1-70K). [Source: SWISSPROT; Acc: P08621] CaMax: BTB (POZ) DOMAIN CONTAINING 5. 1479 1759b [Source: RefSeq; Acc: NM_017658] CaMax: GOLGI COILED COIL PROTEIN 1. [Source: SWISSPROT; Acc: Q96CN9] 1481 1775a CaMax: GOLGI COILED COIL PROTEIN 1. [Source: SWISSPROT; Acc: Q96CN9] 1481 1775a CaMax: OK/SW-CL.87. [Source: SPTREMBL; Acc: Q8NI68] 1136 1782b CaMax: TRANSCRIPTION FACTOR CP2; TRANSCRIPTION FACTOR CP2, 295 178a ALPHA GLOBIN. [Source: RefSeq; Acc: NM_005653] CaMax: ATP-DEPENDENT CLP PROTEASE ATP-BINDING SUBUNIT CLPX- 89 1801b LIKE, MITOCHONDRIAL PRECURSOR. [Source: SWISSPROT; Acc: O76031] CaMax: TIGGER TRANSPOSABLE ELEMENT DERIVED 1; JERKY (MOUSE) 472 180a HOMOLOG-LIKE. [Source: RefSeq; Acc: NM_145702] CaMax: SIALIC ACID BINDING IG-LIKE LECTIN 6 PRECURSOR (SIGLEC-6) 272 1812b (OBESITY-BINDING PROTEIN 1) (OB-BP1) (CD33 ANTIGEN-LIKE 1). [Source: SWISSPROT; Acc: O43699] CaMax: PEPTIDYL-GLYCINE ALPHA-AMIDATING MONOOXYGENASE 39 1814c PRECURSOR (EC 1.14.17.3) (PAM). [Source: SWISSPROT; Acc: P19021] CaMax: PROTEOGLYCAN LINK PROTEIN PRECURSOR (CARTILAGE LINK 1283 1828b PROTEIN) (LP). [Source: SWISSPROT; Acc: Q9QUP5] CaMax: SPLICEOSOMAL PROTEIN SAP155 (FRAGMENT). 263 1853a [Source: SPTREMBL; Acc: Q9ET34] CaMax: CYTOCHROME B5. [Source: SWISSPROT; Acc: P00173] 15 1857c CaMax: MYELOID/LYMPHOID OR MIXED-LINEAGE LEUKEMIA 3; ALR- 983 1859a LIKE PROTEIN. [Source: RefSeq; Acc: NM_021230] CaMax: SNF2 HISTONE LINKER PHD RING HELICASE. 133 1917f [Source: RefSeq; Acc: NM_173082] CaMax: ENDOTHELIAL AND SMOOTH MUSCLE CELL-DERIVED 150 1919a NEUROPILIN-LIKE PROTEIN; COAGULATION FACTOR V/VIII- HOMOLOGY DOMAINS PROTEIN 1. [Source: RefSeq; Acc: NM_080927] CaMax: BETA-TUBULIN COFACTOR E. [Source: RefSeq; Acc: NM_003193] 24 1940e CaMax: CDW92 ANTIGEN; CHOLINE TRANSPORTER-LIKE PROTEIN. 314 1941e [Source: RefSeq; Acc: NM_080546] CaMax: ALPHA-ACTININ-2-ASSOCIATED LIM PROTEIN; ENIGMA 338 1943a HOMOLOG. [Source: RefSeq; Acc: NM_014476] CaMax: VAV-3 PROTEIN. [Source: SWISSPROT; Acc: Q9UKW4] 1293 1950a CaMax: NGFI-A BINDING PROTEIN 1 (EGR-1 BINDING PROTEIN 1) 371 1953a (TRANSCRIPTIONAL REGULATORY PROTEIN P54). [Source: SWISSPROT; Acc: Q13506] CaMax: MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 1494 1961e INTERACTING PROTEIN (MADH-INTERACTING PROTEIN) (SMAD ANCHOR FOR RECEPTOR ACTIVATION) (RECEPTOR ACTIVATION ANCHOR) (HSARA) (NOVEL SERINE PROTEASE) (NSP). [Source: SWISSPROT; Acc: O95405] CaMax: ANTIGEN PEPTIDE TRANSPORTER 2 (APT2) (PEPTIDE 1083 1967a TRANSPORTER TAP2) (PEPTIDE TRANSPORTER PSF2) (PEPTIDE SUPPLY FACTOR 2) (PSF-2) (PEPTIDE TRANSPORTER INVOLVED IN ANTIGEN PROCESSING 2). [Source: SWISSPROT; Acc: Q03519] CaMax: PELLINO PROTEIN. [Source: RefSeq; Acc: NM_020651] 1084 1968a CaMax: COLLAGEN ALPHA 1(XI) CHAIN PRECURSOR. 1088 1982a [Source: SWISSPROT; Acc: P12107] CaMax: MICROTUBULE-ASSOCIATED PROTEIN, RP/EB FAMILY, MEMBER 1092 1990a 2; T-CELL ACTIVATION PROTEIN, EB1 FAMILY; APC-BINDING PROTEIN EB1. [Source: RefSeq; Acc: NM_014268] CaMax: PINS. [Source: RefSeq; Acc: NM_029522] 1498 2008a CaMax: NUCLEAR FACTOR RIP140 (NUCLEAR RECEPTOR INTERACTING 1499 2013a PROTEIN 1). [Source: SWISSPROT; Acc: P48552] CaMax: 60S RIBOSOMAL PROTEIN L4 (L1). [Source: SWISSPROT; Acc: P36578] 233 2015e CaMax: MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 284 2020b KINASE 3 (EC 2.7.1.37) (MAPK/ERK KINASE KINASE KINASE 3) (MEK KINASE KINASE 3) (MEKKK 3) (GERMINAL CENTER KINASE RELATED PROTEIN KINASE) (GLK). [Source: SWISSPROT; Acc: Q8IVH8] CaMax: LATE ENVELOPE PROTEIN 4. [Source: RefSeq; Acc: NM_178352] 1501 2034a CaMax: DNA-DIRECTED RNA POLYMERASES III 12.5 KDA POLYPEPTIDE 149 2035d (EC 2.7.7.6) (RNA POLYMERASE III C11 SUBUNIT) (HSC11P) (HRPC11) (MY010 PROTEIN). [Source: SWISSPROT; Acc: Q9Y2Y1] CaMax: POTENTIAL HELICASE WITH ZINC-FINGER DOMAIN. 1305 2056d [Source: SWISSPROT; Acc: P42694] CaMax: PALLADIN; CGI-151 PROTEIN. [Source: RefSeq; Acc: NM_016081] 1307 2070a CaMax: POTENTIAL PHOSPHOLIPID-TRANSPORTING ATPASE IA (EC 99 2074b 3.6.3.1) (CHROMAFFIN GRANULE ATPASE II) (ATPASE CLASS I TYPE 8A MEMBER 1). [Source: SWISSPROT; Acc: Q9Y2Q0] CaMax: SEPTIN 7 (CDC10 PROTEIN HOMOLOG). 1098 2078a [Source: SWISSPROT; Acc: Q16181] CaMax: WD REPEAT AND FYVE DOMAIN CONTAINING 1 ISOFORM 1; 113 2083e PHOSPHOINOSITIDE-BINDING PROTEIN SR1; WD40 AND FYVE DOMAIN CONTAINING 1. [Source: RefSeq; Acc: NM_020830] CaMax: FIBRILLIN 1 PRECURSOR. [Source: SWISSPROT; Acc: P35555] 1104 2100b CaMax: ZINC FINGER PROTEIN 345 (ZINC FINGER PROTEIN HZF10). 989 2110a [Source: SWISSPROT; Acc: Q14585] CaMax: MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 1. 505 211b [Source: SWISSPROT; Acc: P33527] CaMax: PEPTIDE-HISTIDINE TRANSPORTER 4. 1557 2123a [Source: RefSeq; Acc: NM_145648] CaMax: SMALL PROTEIN EFFECTOR 1 OF CDC42. 990 2129a [Source: RefSeq; Acc: NM_020239] CaMax: PROTEOGLYCAN 4; MEGAKARYOCYTE STIMULATING FACTOR; 215 2224a PROTEOGLYCAN 4, (MEGAKARYOCYTE STIMULATING FACTOR, ARTICULAR SUPERFICIAL ZONE PROTEIN); JACOBS CAMPTODACTYLY-ARTHIROPATHY-PERICARDITIS SYNDROME; CAMPTODACTYLY, ARTHROPATHY, COXA VARA, PERICARDITIS SYNDROME. [Source: RefSeq; Acc: NM_005807] CaMax: THYROTROPIN-RELEASING HORMONE RECEPTOR (TRH-R) 994 2234a (THYROLIBERIN RECEPTOR). [Source: SWISSPROT; Acc: P21761] CaMax: CGMP-INHIBITED 3′,5′-CYCLIC PHOSPHODIESTERASE A (EC 996 2238a 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE A) (CGI- PDE A). [Source: SWISSPROT; Acc: Q14432] CaMax: CGMP-INHIBITED 3′,5′-CYCLIC PHOSPHODIESTERASE A (EC 188 2241a 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE A) (CGI- PDE A). [Source: SWISSPROT; Acc: Q14432] CaMax: CGMP-INHIBITED 3′,5′-CYCLIC PHOSPHODIESTERASE A (EC 996 2238a 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE A) (CGI- PDE A). [Source: SWISSPROT; Acc: Q14432] CaMax: THROMBOSPONDIN 1 PRECURSOR. 999 2267a [Source: SWISSPROT; Acc: P07996] CaMax: CGMP-INHIBITED 3′,5′-CYCLIC PHOSPHODIESTERASE A (EC 188 2241a 3.1.4.17) (CYCLIC GMP INHIBITED PHOSPHODIESTERASE A) (CGI- PDE A). [Source: SWISSPROT; Acc: Q14432] CaMax: THROMBOSPONDIN 1 PRECURSOR. 206 2374a [Source: SWISSPROT; Acc: P07996] CaMax: SPECTRIN ALPHA CHAIN, BRAIN (SPECTRIN, NON-ERYTHROID 530 239a ALPHA CHAIN) (ALPHA-II SPECTRIN) (FODRIN ALPHA CHAIN). [Source: SWISSPROT; Acc: Q13813] CaMax: GLUCOCORTICOID MODULATORY ELEMENT BINDING PROTEIN 90 23a 1 (GMEB-1) (PARVOVIRUS INITIATION FACTOR P96) (PIF P96) (DNA BINDING PROTEIN P96PIF). [Source: SWISSPROT; Acc: Q9Y692] CaMax: TENASCIN PRECURSOR (TN) (HEXABRACHION) (CYTOTACTIN) 553 267d (NEURONECTIN) (GMEM) (JI) (MIOTENDINOUS ANTIGEN) (GLIOMA-ASSOCIATED-EXTRACELLULAR MATRIX ANTIGEN) (GP 150-225) (TENASCIN-C) (TN-C). [Source: SWISSPROT; Acc: P24821] CaMax: ELAC HOMOLOG 1. [Source: RefSeq; Acc: NM_018696] 116 272d CaMax: PROTEIN CGI-147. [Source: SWISSPROT; Acc: Q9Y3E5] 598 307b CaMax: RETINAL PIGMENT EPITHELIUM-SPECIFIC PROTEIN 65 KDA; 597 308c RETINAL PIGMENT EPITHELIUM-SPECIFIC PROTEIN (65 KD); RETINITIS PIGMENTOSA 20 (AUTOSOMAL RECESSIVE). [Source: RefSeq; Acc: NM_000329] CaMax: EXOCYST COMPLEX COMPONENT SEC3 (BM-012). 1532 320a [Source: SWISSPROT; Acc: Q9NV70] CaMax: MICROSOMAL SIGNAL PEPTIDASE 18 KDA SUBUNIT (EC 3.4.—.—) 71 326e (SPASE 18 KDA SUBUNIT) (SPC18) (ENDOPEPTIDASE SP18). [Source: SWISSPROT; Acc: Q9R0P6] CaMax: PALLADIN; CGI-151 PROTEIN. [Source: RefSeq; Acc: NM_016081] 591 328b CaMax: FERRITIN HEAVY CHAIN (FERRITIN H SUBUNIT). 440 106a [Source: SWISSPROT; Acc: P02794] CaMax: RNA-BINDING PROTEIN EWS (EWS ONCOGENE) (EWING 640 364a SARCOMA BREAKPOINT REGION 1 PROTEIN). [Source: SWISSPROT; Acc: Q01844] CaMax: ACIDIC LEUCINE-RICH NUCLEAR PHOSPHOPROTEIN 32 FAMILY 644 374a MEMBER B (PHAPI2 PROTEIN) (SILVER-STAINABLE PROTEIN SSP29) (ACIDIC PROTEIN RICH IN LEUCINES). [Source: SWISSPROT; Acc: Q92688] CaMax: FIP1-LIKE 1; REARRANGED IN HYPEREOSINOPHILIA. 423 38a [Source: RefSeq; Acc: NM_030917] CaMax: EUKARYOTIC TRANSLATION INITIATION FACTOR 2 SUBUNIT 1 913 415b (EUKARYOTIC TRANSLATION INITIATION FACTOR 2 ALPHA SUBUNIT) (EIF-2-ALPHA) (EIF-2ALPHA) (EIF-2A). [Source: SWISSPROT; Acc: P05198] CaMax: NUCLEAR FACTOR OF ACTIVATED T CELLS 5 (T CELL 658 459a TRANSCRIPTION FACTOR NFAT5) (NF-AT5) (TONICITY- RESPONSIVE ENHANCER-BINDING PROTEIN) (TONE-BINDING PROTEIN) (TONEBP). [Source: SWISSPROT; Acc: O94916] CaMax: ADENYLOSUCCINATE SYNTHETASE (EC 6.3.4.4) (IMP-- 292 464b ASPARTATE LIGASE) (ADSS) (AMPSASE). [Source: SWISSPROT; Acc: P30520] CaMax: SURFACE GLYCOPROTEIN, IG SUPERFAMILY MEMBER. 193 465b [Source: RefSeq; Acc: NM_016952] CaMax: T-COMPLEX ASSOCIATED-TESTIS-EXPRESSED 1-LIKE (PROTEIN 662 478a 91/23). [Source: SWISSPROT; Acc: P51808] CaMax: T-COMPLEX ASSOCIATED-TESTIS-EXPRESSED 1-LIKE (PROTEIN 129 479c 91/23). [Source: SWISSPROT; Acc: P51808] CaMax: RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 2 (GEF-H1 668 487a PROTEIN) (PROLIFERATING CELL NUCLEOLAR ANTIGEN P40). [Source: SWISSPROT; Acc: Q92974] CaMax: HEXOKINASE, TYPE II (EC 2.7.1.1) (HK II) (MUSCLE FORM 669 488a HEXOKINASE). [Source: SWISSPROT; Acc: P52789] CaMax: BTB (POZ) DOMAIN CONTAINING 5. 622 520a [Source: RefSeq; Acc: NM_017658] CaMax: MYOCYTE-SPECIFIC ENHANCER FACTOR 2C. 621 521b [Source: SWISSPROT; Acc: Q06413] CaMax: PROTEASOME SUBUNIT ALPHA TYPE 3 (EC 3.4.25.1) 9 530b (PROTEASOME COMPONENT C8) (MACROPAIN SUBUNIT C8) (MULTICATALYTIC ENDOPEPTIDASE COMPLEX SUBUNIT C8). [Source: SWISSPROT; Acc: P25788] CaMax: HDCMD38P. [Source: SPTREMBL; Acc: Q9P1S5] 612 539a CaMax: TRANSMEMBRANE PROTEIN 4. [Source: RefSeq; Acc: NM_014255] 670 545a CaMax: SER/ARG-RELATED NUCLEAR MATRIX PROTEIN (PLENTY OF 1403 550a PROLINES 101-L; SER/ARG-RELATED NUCLEAR MATRIX PROTEIN (PLENTY OF PROLINES 101-LIKE). [Source: RefSeq; Acc: NM_005839] CaMax: F-BOX AND LEUCINE-RICH REPEAT PROTEIN 3A; F-BOX PROTEIN 114 555b FBL3A. [Source: RefSeq; Acc: NM_012158] CaMax: ECHINODERM MICROTUBULE-ASSOCIATED PROTEIN-LIKE 4 673 571a (EMAP-4) (RESTRICTEDLY OVEREXPRESSED PROLIFERATION- ASSOCIATED PROTEIN) (ROPP 120). [Source: SWISSPROT; Acc: Q9HC35] CaMax: SPLICING FACTOR, ARGININE/SERINE-RICH 6 (PRE-MRNA 676 579a SPLICING FACTOR SRP55). [Source: SWISSPROT; Acc: Q13247] CaMax: INTEGRIN ALPHA-6 PRECURSOR (VLA-6) (CD49F). 417 57a [Source: SWISSPROT; Acc: P23229] CaMax: LBP-9. [Source: RefSeq; Acc: NM_014553] 80 581a CaMax: FETAL ALZHEIMER ANTIGEN (FETAL ALZ-50-REACTIVE CLONE 312 597c 1). [Source: SWISSPROT; Acc: Q12830] CaMax: RAS GTPASE-ACTIVATING-LIKE PROTEIN IQGAP1 (P195). 1022 623a [Source: SWISSPROT; Acc: P46940] CaMax: KREMEN PROTEIN 1 PRECURSOR (KRINGLE-CONTAINING 1046 628a PROTEIN MARKING THE EYE AND THE NOSE) (DICKKOPF RECEPTOR). [Source: SWISSPROT; Acc: Q96MU8] CaMax: SER/ARG-RELATED NUCLEAR MATRIX PROTEIN (PLENTY OF 1404 635a PROLINES 101-L; SER/ARG-RELATED NUCLEAR MATRIX PROTEIN (PLENTY OF PROLINES 101-LIKE). [Source: RefSeq; Acc: NM_005839] CaMax: T-COMPLEX ASSOCIATED-TESTIS-EXPRESSED 1-LIKE (PROTEIN 261 638b 91/23). [Source: SWISSPROT; Acc: P51808] CaMax: UPF0183 PROTEIN. [Source: SWISSPROT; Acc: Q9BSU1] 683 685a CaMax: TIGGER TRANSPOSABLE ELEMENT DERIVED 1; JERKY (MOUSE) 688 692a HOMOLOG-LIKE. [Source: RefSeq; Acc: NM_145702] CaMax: INVERSIN. [Source: RefSeq; Acc: NM_014425] 697 704b CaMax: INVERSIN. [Source: RefSeq; Acc: NM_014425] 697 704b CaMax: COLLAGEN ALPHA 1(X) CHAIN PRECURSOR. 701 710a [Source: SWISSPROT; Acc: Q03692] CaMax: GRAVE'S DISEASE CARRIER PROTEIN (GDC) (GRAVE'S DISEASE 1405 726b AUTOANTIGEN) (GDA) (MITOCHONDRIAL SOLUTE CARRIER PROTEIN HOMOLOG). [Source: SWISSPROT; Acc: P16260] CaMax: DIAMINE ACETYLTRANSFERASE (BC 2.3.1.57) 142 736a (SPERMIDINE/SPERMINE N(1)-ACETYLTRANSFERASE) (SSAT) (PUTRESCINE ACETYLTRANSFERASE). [Source: SWISSPROT; Acc: P21673] CaMax: HISTIDINE-RICH MEMBRANE PROTEIN KE4. 408 73b [Source: SWISSPROT; Acc: Q92504] CaMax: IDN3 PROTEIN ISOFORM A. [Source: RefSeq; Acc: NM_133433] 126 747a CaMax: MAJOR PRION PROTEIN PRECURSOR (PRP) (PRP27-30) (PRP33-35C) 268 785b (ASCR) (CD230 ANTIGEN). [Source: SWISSPROT; Acc: P04156] CaMax: SARCOSPAN (K-RAS ONCOGENE-ASSOCIATED PROTEIN) 372 794a (KIRSTEN-RAS-ASSOCIATED PROTEIN). [Source: SWISSPROT; Acc: Q14714] CaMax: NITROGEN FIXATION CLUSTER-LIKE. 72 85.1c [Source: RefSeq; Acc: NM_014301] CaMax: BRANCHED-CHAIN AMINO ACID AMINOTRANSFERASE, 1130 856c CYTOSOLIC (EC 2.6.1.42) (BCAT(C)) (ECA39 PROTEIN). [Source: SWISSPROT; Acc: P54687] CaMax: ZINC FINGER PROTEIN SLUG (NEURAL CREST TRANSCRIPTION 916 863c FACTOR SLUG) (SNAIL HOMOLOG 2). [Source: SWISSPROT; Acc: P97469] CaMax: RAS-RELATED PROTEIN RAB-6A (RAB-6). 161 890a [Source: SWISSPROT; Acc: P20340] CaMax: PEPTIDYL-GLYCINE ALPHA-AMIDATING MONOOXYGENASE 786 909a PRECURSOR (EC 1.14.17.3) (PAM). [Source: SWISSPROT; Acc: P19021] CaMax: HEAT SHOCK PROTEIN HSP 90-BETA (HSP 84) (TUMOR SPECIFIC 400 90c TRANSPLANTATION 84 KDA ANTIGEN) (TSTA). [Source: SWISSPROT; Acc: P11499] CaMax: MYELIN GENE EXPRESSION FACTOR 2. 777 919b [Source: RefSeq; Acc: NM_016132] CaMax: NUCLEAR RECEPTOR COACTIVATOR 1 ISOFORM 1. 398 92c [Source: RefSeq; Acc: NM_003743] CaMax: CHURCHILL PROTEIN (MY015 PROTEIN). 767 935b [Source: SWISSPROT; Acc: Q8WUH1] CaMax: 6.8 KDA MITOCHONDRIAL PROTEOLIPID. 759 953a [Source: SWISSPROT; Acc: P56379] CaMax: PUMILIO HOMOLOG 1. [Source: RefSeq; Acc: NM_014676] 755 963c CaMax: G1/S-SPECIFIC CYCLIN D2. [Source: SWISSPROT; Acc: P30279] 1423 986a CaMax: TRANSCRIPTION FACTOR SOX-9. [Source: SWISSPROT; Acc: P48436] 194 990a CaMax: INHIBITOR OF BRUTON'S TYRSOINE KINASE; BTK-BINDING 257 994b PROTEIN. [Source: RefSeq; Acc: NM_015525] CaMax: 40S RIBOSOMAL PROTEIN S20. [Source: SWISSPROT; Acc: P17075] 930 996a

EXAMPLE 3 Preparation of Microarray

Microarray probes were generated by PCR-amplifying clones isolated from differential display. Probes were spotted in duplicate onto poly-L-lysine coated slides using a GMS417 (Affymetrix) arrayer. Osteoarthritic cartilage samples were obtained from the femoral heads of clinically diagnosed canines undergoing total flip replacement. RNA was hybridized to the slides using the HC ExpressArray (Digene) kit and visualized using a GMS418 (Affymetrix) scanner. The Imagene (Biodiscovery) program was used for spot finding and subsequent data analysis was performed using GeneSight (Biodiscovery). Expression levels are represented after background subtraction, log(base 2) transformation and global slide signal normalization.

Microarray Clone Preparation

Culture blocks containing 1.5 mLs of Magnificent Broth (MB) plus tetracycline (50 mg/mL) were inoculated with appropriate clones from glycerol stocks and grown overnight with shaking at 37° C. These cultures were used to inoculate a second culture block that was grown for approximately 6 hours with shaking at 37° C. These 6-hour cultures were used to inoculate 2 replicate culture blocks which were grown overnight with shaking at 37° C. Cultures were centrifuged to pellet cells and plasmids isolated using the Qiagen 96-well culture system (Qiagen). Plasmid concentrations were determined using a spectrophotometer by measuring the absorbance at 260 nm. All cDNA plasmid clones were amplified in duplicate using the following PCR reaction (final concentration): 10×PCR buffer (10 mM Tris-HCl, pH 8.3, 50 mM KCl, 2.5 mM MgCl₂), 500 uM ea. dNTP, 600 nM Rgh primer, 600 nM Lgh primer, 1 μL (5 units/μL) of Eppendorf Taq polymerase and 1 μL (˜100 ng/μL) cDNA template in a total of 100 μL. The reaction was performed in the following conditions: 94° C. 30 seconds, 52° C. 40 seconds, 72° C. 1 minute for 40 cycles, followed by 72° C.-5 min and 4° C.-hold. Amplified products were verified on 1.5% agarose gel and purified using Minelute (Qiagen) protocol. The 200 μL of PCR was added to the filter plate and vacuum was turned on to pull through all PCR reagents and liquid leaving only the cDNA bound to the filter. 30 μL molecular grade water was added to the filter plate and incubated at room temperature on an orbital shaker at 900 rpm for 5 minutes. The supernatant containing the purified cDNA was aspirated from the filter plate. The cDNA's were dried for 2 hrs or to completion in a speed vac at 45° C. 30 μL Corning Universal Printing Buffer was added to all cDNA's and resuspended over night at room temperature on an orbital shaker. 2 μL's transferred for concentration analysis and the appropriate amount of Corning Universal Printing Buffer was added for a final concentration of 200 to 500 ng/uL. Plates were stored at −20° C. until and after each array printing.

Clone Arraying

Microscope slides (Goldseal cat #3010) were submerged in a 10% NaOH (Fisher cat # S318-500) 57% EtOH solution and incubated at room temperature in an orbital shaker at 50 rpm for 2 hours. Slides were rinsed in Milli-Q water 5× for 30 seconds each. While the slides remain in the last water rinse a 10% Poly-L-Lysine (Sigma cat # P8920), 10% 1×PBS (GibcoBRL cat#70013-032) was brought to 700 mLs using Milli-Q water in plastic ware. Slides were submerged in coating solution and incubated at room temperature in orbital shaker at 50 rpm for 1 hour. Slides were rinsed in Milli-Q water 5× for 30 seconds each and spun at 500 rpm for 1 minute. Slides were incubated in 55° C. oven for 10 min and kept in dessicator for at least 14 days and no longer than 3 months prior to arraying. cDNA clones were arrayed using the GMS 417 arrayer (Affymetrix). All slides were placed in a room temperature dessicator to dry overnight. The slides were rehydrated over boiling Milli-Q water (steam) and snap dried DNA side up on an 80° C. heat block. To ensure efficient cross-linking the slides were baked for 2 hours at 80° C. in an oven and then cross-linked with Stratalinker (120 mJ, Stratagene). All slides were stored in a room temperature dessicator until used for cDNA hybridization.

cDNA Microarray Hybridization

All RNA samples were reverse transcribed using the following reaction: 5× Superscript II First Strand Buffer (Invitrogen), 1 uL (1 pmole/uL) of RT primer (Genisphere), 1 uL Superase-In™ Rnase inhibitor, 1 uL 10 mM ea. DNTP, 2 uL 0.1 M DTT, 1 uL Superscript II and 5 ug total RNA. The reaction was performed at 42° C. for 2 hrs. The reaction was stopped by adding 3.5 uL of 0.5 M NaOH/50 mM EDTA and incubating at 65° C. for 10 minutes. The reaction was neutralized by adding 5 uL of 1M Tris-HCL, pH 7.5. 101.5 uL of 10 mM Tris, pH 8, 1 mM EDTA was added and the cDNA was purified and concentrated by following the Microcon YM-30 (Millipore) protocol. The concentrated cDNA was brought to a final volume of 10 uL with Nuclease-free water and the following reagents added: 20 ul of 2× hybridization buffer (Genisphere), 2 uL dT LNA blocker and 8 uL Nuclease-free water for a total of 40 uL. The hybridization mixture was heated at 80° C. for 10 minutes and loaded onto the microarray slide at the edge of the lifterSlip. The slide was then placed into a GeneMachines dual hybridization chamber and placed in a 60° C. water bath overnight. The following day the slides were processed according to the 3DNA Array 350 (Genisphere) protocol. Briefly, the slides were washed (2×SSC-0.2% SDS, 2×SSC, 0.2×SSC), spun dry at 1000 rpm for 1 min and the 3DNA capture hybridization performed. The slides were washed (2×SSC-0.2% SDS, 2×SSC, 0.2×SSC) spun dry at 1000 rpm for 1 min and scanned using a GMS 418 array scanner (Affymetrix).

Microarray Analysis

Scanned images representing RNA transcripts bound to specific clones were quantified and checked for spot quality control using Imagene analysis software (BioDiscovery). Quantified images were analyzed using Genesight analysis software (BioDiscovery). The analysis represented subtraction of background surrounding the spots, averaging spot replicates, deletion of clone information representing clone hybridization signals not greater than 200 above background on all samples, log (base 2) transformation and global normalization of each slide (values expressed as percent of average spot intensity).

EXAMPLE 4 Expression Analysis Using Microarray

RNA was extracted from cartilage as described, supra. Microarray analysis (described supra) was performed on 8 osteoarthritic cartilage samples from clinically diagnosed canines undergoing total hip replacement and 8 normal cartilage samples. A standard T-test (two categories) was performed on the final hybridization signals for osteoarthlitic characterization of cartilage samples (p<0.05 and p<0.01, results shown in Tables 3 and 4, respectively).

TABLE 3 Normal Gene ID OA AVG STD AVG STD DIF(OA-N) Fold 1028c 1.81 0.75 0.24 0.94 1.57 2.96 768a 1.99 0.54 0.88 0.55 1.11 2.16 141c 3.94 0.57 3.01 0.75 0.93 1.90 154a 0.80 0.85 0.06 0.56 0.74 1.67 1548c 5.49 0.41 4.79 0.46 0.69 1.62 718a 5.93 0.66 5.29 0.43 0.64 1.56 11b −0.85 0.66 −1.46 0.30 0.60 1.52 363a −0.24 0.52 −0.77 0.44 0.53 1.45 370a 6.06 0.46 5.54 0.61 0.51 1.43 1551a 0.71 0.51 0.23 0.49 0.48 1.40 376a −0.66 0.42 −1.01 0.24 0.36 1.28 84.2c 0.39 0.35 0.04 0.28 0.36 1.28 380a −1.61 0.22 −1.84 0.18 0.24 1.18 372a 0.11 0.25 −0.12 0.23 0.23 1.17 2148a −1.81 0.23 −1.62 0.15 −0.20 1.15 1800a −2.23 0.16 −1.98 0.24 −0.25 1.19 1357a −2.01 0.12 −1.73 0.07 −0.28 1.21 168c 5.11 0.19 5.40 0.21 −0.29 1.22 1090d 6.26 0.22 6.55 0.23 −0.29 1.22 60a −0.18 0.34 0.11 0.25 −0.29 1.22 96e 5.50 0.16 5.80 0.35 −0.30 1.23 2015e 4.67 0.24 4.97 0.23 −0.30 1.23 383d −1.78 0.18 −1.47 0.14 −0.30 1.24 128a 2.10 0.39 2.41 0.24 −0.31 1.24 621b −2.03 0.27 −1.72 0.35 −0.32 1.25 1174d −0.45 0.36 −0.12 0.18 −0.33 1.25 947a 0.71 0.29 1.04 0.27 −0.33 1.26 1964a −2.34 0.18 −2.01 0.27 −0.33 1.26 619b −2.11 0.21 −1.77 0.23 −0.34 1.26 2222b −0.52 0.31 −0.18 0.33 −0.34 1.27 1468c −1.26 0.28 −0.91 0.32 −0.34 1.27 1629a −0.78 0.36 −0.44 0.17 −0.34 1.27 174a −0.22 0.27 0.13 0.38 −0.35 1.27 2085c 3.62 0.47 3.97 0.16 −0.35 1.27 1461a −1.73 0.26 −1.38 0.24 −0.35 1.27 764b 1.37 0.34 1.73 0.32 −0.36 1.28 731a 1.61 0.37 1.98 0.36 −0.36 1.28 1051a 2.30 0.34 2.67 0.36 −0.36 1.29 613a −2.07 0.24 −1.70 0.30 −0.37 1.29 531a −0.52 0.20 −0.15 0.36 −0.37 1.29 1471a −1.75 0.35 −1.38 0.24 −0.37 1.30 1381a 6.20 0.33 6.57 0.26 −0.38 1.30 44c 4.99 0.36 5.37 0.31 −0.38 1.30 1892a −0.02 0.25 0.36 0.38 −0.38 1.30 76b −0.54 0.41 −0.16 0.19 −0.38 1.30 366a −1.98 0.32 −1.60 0.20 −0.38 1.30 994b −1.82 0.43 −1.44 0.24 −0.39 1.31 1954e −1.85 0.20 −1.46 0.35 −0.39 1.31 2127c 0.08 0.23 0.48 0.31 −0.39 1.31 530b 1.39 0.21 1.78 0.23 −0.40 1.32 409a −1.18 0.34 −0.78 0.38 −0.40 1.32 2120a 1.36 0.41 1.76 0.41 −0.40 1.32 1405c 3.41 0.34 3.81 0.16 −0.41 1.32 1765a −1.60 0.28 −1.19 0.28 −0.41 1.33 638b −1.51 0.31 −1.11 0.38 −0.41 1.33 329d −2.04 0.47 −1.63 0.26 −0.41 1.33 1853a 1.27 0.40 1.68 0.44 −0.41 1.33 2247a −0.56 0.44 −0.15 0.32 −0.41 1.33 166a −0.97 0.34 −0.56 0.25 −0.41 1.33 1746a 1.41 0.43 1.83 0.31 −0.41 1.33 1797a −1.79 0.25 −1.38 0.30 −0.42 1.33 1729a 3.95 0.37 4.37 0.23 −0.42 1.34 1857c −0.91 0.16 −0.49 0.20 −0.42 1.34 1081a −1.83 0.20 −1.41 0.38 −0.42 1.34 2002c −0.35 0.35 0.08 0.37 −0.42 1.34 785b 0.98 0.41 1.40 0.42 −0.42 1.34 1092b −1.84 0.32 −1.41 0.41 −0.42 1.34 1784a −2.32 0.38 −1.89 0.35 −0.43 1.34 523a −1.36 0.28 −0.93 0.32 −0.43 1.34 2172c −2.54 0.17 −2.11 0.11 −0.43 1.35 58a −0.09 0.22 0.34 0.24 −0.43 1.35 411b −1.73 0.44 −1.30 0.28 −0.43 1.35 1511b −2.18 0.35 −1.75 0.41 −0.43 1.35 1812b −2.11 0.23 −1.68 0.25 −0.43 1.35 1885c −1.53 0.35 −1.09 0.45 −0.43 1.35 1619a −1.58 0.41 −1.14 0.40 −0.43 1.35 2344a −1.74 0.27 −1.30 0.51 −0.43 1.35 244a −1.91 0.01 −1.47 0.12 −0.44 1.35 70d −1.65 0.30 −1.21 0.34 −0.44 1.36 1477a 2.42 0.56 2.86 0.31 −0.44 1.36 1472a 0.07 0.40 0.51 0.23 −0.44 1.36 452a −0.80 0.33 −0.36 0.21 −0.45 1.36 360a −2.11 0.42 −1.66 0.22 −0.45 1.36 1481c −1.53 0.19 −1.09 0.32 −0.45 1.36 568a 4.36 0.31 4.80 0.42 −0.45 1.36 1940e −0.44 0.30 0.01 0.20 −0.45 1.36 1109a −2.20 0.47 −1.75 0.18 −0.45 1.37 1930a −2.00 0.27 −1.54 0.37 −0.45 1.37 1282b −1.50 0.47 −1.04 0.35 −0.46 1.37 739a −0.46 0.27 0.00 0.15 −0.46 1.37 1276a −1.63 0.43 −1.17 0.51 −0.46 1.38 1728a −0.95 0.47 −0.49 0.26 −0.46 1.38 1923b −1.83 0.20 −1.37 0.36 −0.46 1.38 2020b −2.44 0.43 −1.97 0.28 −0.46 1.38 556b −0.33 0.54 0.13 0.43 −0.47 1.38 1711a −1.92 0.24 −1.45 0.44 −0.47 1.38 49a −1.19 0.37 −0.72 0.35 −0.47 1.38 1271a −1.92 0.26 −1.45 0.36 −0.47 1.39 1612a −0.56 0.41 −0.09 0.28 −0.47 1.39 1497c −2.07 0.35 −1.59 0.35 −0.47 1.39 14a −0.93 0.24 −0.45 0.30 −0.47 1.39 967b −1.87 0.33 −1.39 0.42 −0.48 1.39 1727a −1.68 0.31 −1.20 0.27 −0.48 1.39 1329a −1.64 0.39 −1.16 0.51 −0.48 1.39 464b −1.51 0.52 −1.04 0.21 −0.48 1.39 1490a 0.50 0.47 0.98 0.32 −0.48 1.40 188b −1.65 0.31 −1.17 0.46 −0.48 1.40 178a −1.99 0.31 −1.51 0.48 −0.48 1.40 631b −2.23 0.00 −1.75 0.25 −0.48 1.40 1244b −2.03 0.35 −1.55 0.42 −0.48 1.40 1220b 2.96 0.46 3.44 0.15 −0.48 1.40 758b −0.39 0.43 0.09 0.31 −0.48 1.40 1807a −2.60 0.18 −2.11 0.31 −0.49 1.40 33a 1.31 0.22 1.80 0.35 −0.49 1.40 276a −1.80 0.40 −1.31 0.16 −0.49 1.40 204a −1.25 0.50 −0.76 0.45 −0.49 1.40 543a −2.07 0.39 −1.58 0.37 −0.49 1.40 1764a −0.26 0.37 0.23 0.41 −0.49 1.40 711a 4.68 0.49 5.17 0.48 −0.49 1.41 35c −0.93 0.53 −0.44 0.29 −0.49 1.41 1401c −1.65 0.43 −1.16 0.48 −0.49 1.41 3c −1.75 0.40 −1.26 0.45 −0.49 1.41 494a −1.49 0.40 −1.00 0.38 −0.50 1.41 1146a 0.55 0.33 1.04 0.34 −0.50 1.41 1616a −1.25 0.43 −0.76 0.47 −0.50 1.41 1070b −1.99 0.51 −1.49 0.10 −0.50 1.41 1738b −1.57 0.25 −1.07 0.36 −0.50 1.41 1928a 4.38 0.63 4.88 0.35 −0.50 1.41 597c −1.06 0.49 −0.56 0.28 −0.50 1.41 810a −2.11 0.30 −1.61 0.28 −0.50 1.42 1505c 1.43 0.63 1.93 0.30 −0.50 1.42 1941e −1.88 0.28 −1.38 0.54 −0.51 1.42 742a −2.26 0.51 −1.75 0.26 −0.51 1.42 1993b −1.33 0.38 −0.82 0.34 −0.51 1.42 1299c −2.39 0.42 −1.88 0.40 −0.51 1.42 1960a −1.43 0.54 −0.91 0.42 −0.51 1.43 1191a 0.47 0.53 0.99 0.35 −0.52 1.43 2147a −1.63 0.41 −1.11 0.33 −0.52 1.43 562a −2.16 0.44 −1.64 0.27 −0.52 1.43 1678a 6.05 0.47 6.57 0.26 −0.52 1.44 2223a 5.99 0.52 6.52 0.26 −0.52 1.44 2099a −1.06 0.44 −0.53 0.43 −0.52 1.44 342a −1.81 0.48 −1.28 0.41 −0.52 1.44 56a 3.79 0.23 4.32 0.38 −0.53 1.44 1347b −2.05 0.45 −1.52 0.51 −0.53 1.45 738b −1.75 0.52 −1.22 0.45 −0.54 1.45 1744a 0.72 0.61 1.26 0.23 −0.54 1.45 1814c −1.03 0.40 −0.49 0.37 −0.54 1.45 1918a −1.56 0.23 −1.02 0.65 −0.54 1.45 129b 0.47 0.26 1.01 0.26 −0.54 1.45 1924a −0.46 0.34 0.08 0.41 −0.54 1.45 1060a −1.90 0.48 −1.36 0.37 −0.54 1.45 557b −1.56 0.24 −1.02 0.39 −0.54 1.45 1254a −0.48 0.46 0.06 0.28 −0.54 1.46 1292c −0.94 0.32 −0.40 0.47 −0.54 1.46 2221c −0.01 0.25 0.53 0.33 −0.54 1.46 490c 4.71 0.34 5.26 0.42 −0.54 1.46 907a −2.23 0.20 −1.68 0.29 −0.55 1.47 1224b −1.32 0.59 −0.76 0.15 −0.56 1.47 469b −0.61 0.31 −0.05 0.29 −0.56 1.47 713a −1.30 0.34 −0.74 0.25 −0.56 1.47 861c −2.49 0.52 −1.93 0.36 −0.56 1.47 1372a 1.49 0.32 2.05 0.30 −0.56 1.47 482a −1.55 0.25 −0.99 0.39 −0.56 1.48 1098a −2.29 0.30 −1.72 0.31 −0.56 1.48 1785a −2.19 0.09 −1.63 0.27 −0.56 1.48 1624b −0.95 0.39 −0.38 0.36 −0.57 1.48 1441d −1.09 0.29 −0.52 0.50 −0.57 1.48 553b −0.76 0.16 −0.19 0.27 −0.57 1.48 2033a −2.11 0.38 −1.54 0.43 −0.57 1.49 2179a −2.12 0.29 −1.55 0.46 −0.57 1.49 1349b −2.15 0.62 −1.58 0.13 −0.57 1.49 1257b −0.76 0.22 −0.18 0.34 −0.58 1.49 1506d −1.45 0.32 −0.88 0.36 −0.58 1.49 1939c −2.37 0.07 −1.79 0.36 −0.58 1.49 2007a −1.93 0.29 −1.35 0.20 −0.58 1.49 715a −2.15 0.46 −1.57 0.38 −0.58 1.50 1621a −1.42 0.26 −0.84 0.55 −0.58 1.50 13a −0.25 0.52 0.33 0.24 −0.58 1.50 1288a −1.12 0.25 −0.53 0.36 −0.58 1.50 379a 3.55 0.61 4.14 0.46 −0.59 1.50 1949a −1.40 0.25 −0.82 0.50 −0.59 1.50 142.2c 1.04 0.28 1.63 0.26 −0.59 1.50 1054a −0.73 0.26 −0.14 0.31 −0.59 1.50 570b 0.13 0.60 0.72 0.27 −0.59 1.50 1504d 0.69 0.55 1.28 0.39 −0.59 1.51 441a −2.05 0.43 −1.46 0.38 −0.59 1.51 1943a −1.74 0.31 −1.14 0.67 −0.59 1.51 1033c −2.47 0.52 −1.88 0.29 −0.59 1.51 1404c 2.76 0.43 3.35 0.29 −0.59 1.51 8a −0.51 0.51 0.08 0.30 −0.60 1.51 46a −0.07 0.54 0.52 0.34 −0.60 1.51 1758a 1.42 0.63 2.02 0.23 −0.60 1.51 1985a −1.92 0.23 −1.33 0.50 −0.60 1.51 326e −0.12 0.25 0.48 0.24 −0.60 1.51 85.1c −0.04 0.40 0.56 0.22 −0.60 1.51 1675a −1.75 0.14 −1.15 0.40 −0.60 1.52 1772a 0.78 0.51 1.38 0.60 −0.60 1.52 1707c −2.25 0.71 −1.64 0.30 −0.60 1.52 1474a −2.38 0.36 −1.78 0.42 −0.60 1.52 574a 0.54 0.26 1.14 0.47 −0.61 1.52 1920a −1.58 0.40 −0.97 0.74 −0.61 1.52 34a −1.29 0.34 −0.68 0.70 −0.61 1.53 2205a −1.01 0.49 −0.40 0.59 −0.61 1.53 1712a 2.61 0.63 3.22 0.60 −0.61 1.53 1010a −2.60 0.42 −1.99 0.31 −0.61 1.53 1382d −1.71 0.09 −1.10 0.71 −0.61 1.53 269b −2.46 0.29 −1.85 0.41 −0.61 1.53 2159b −2.29 0.29 −1.67 0.44 −0.62 1.53 1972a −1.73 0.43 −1.11 0.61 −0.62 1.53 1298a −1.70 0.39 −1.08 0.55 −0.62 1.53 2108b 0.49 0.54 1.10 0.29 −0.62 1.54 567b −0.45 0.57 0.17 0.35 −0.62 1.54 45.1b 4.48 0.51 5.11 0.29 −0.62 1.54 949c −1.76 0.39 −1.14 0.54 −0.62 1.54 1545b −1.84 0.48 −1.22 0.50 −0.63 1.54 2173a 2.84 0.40 3.47 0.49 −0.63 1.55 1676a −1.90 0.07 −1.27 0.47 −0.63 1.55 581a −1.77 0.16 −1.14 0.25 −0.63 1.55 472a 4.26 0.74 4.89 0.42 −0.63 1.55 1695a 0.22 0.30 0.85 0.59 −0.63 1.55 1414b −0.28 0.42 0.35 0.39 −0.64 1.55 151b 0.13 0.48 0.77 0.28 −0.64 1.55 112d 0.04 0.49 0.68 0.40 −0.64 1.56 461a −1.37 0.49 −0.73 0.24 −0.64 1.56 1557a −1.79 0.28 −1.15 0.76 −0.64 1.56 1615b −1.61 0.56 −0.97 0.34 −0.64 1.56 489c 1.81 0.65 2.46 0.29 −0.64 1.56 310h −1.41 0.50 −0.76 0.25 −0.64 1.56 297a −1.13 0.38 −0.48 0.25 −0.64 1.56 1495a −1.30 0.64 −0.66 0.46 −0.64 1.56 1801b −0.24 0.28 0.41 0.38 −0.65 1.56 23a −1.60 0.45 −0.96 0.22 −0.65 1.56 1739a −0.50 0.43 0.14 0.36 −0.65 1.57 170a 1.94 0.28 2.59 0.22 −0.65 1.57 1955a −1.57 0.30 −0.93 0.52 −0.65 1.57 1302a −2.16 0.80 −1.51 0.42 −0.65 1.57 2088a −0.75 0.46 −0.10 0.29 −0.65 1.57 18a 0.01 0.67 0.66 0.39 −0.65 1.57 182a −1.80 0.28 −1.15 0.55 −0.65 1.57 2243b −2.44 0.24 −1.78 0.30 −0.65 1.57 1440a 1.14 0.42 1.79 0.36 −0.65 1.57 2351c −1.39 0.37 −0.74 0.32 −0.65 1.57 1415b −0.73 0.33 −0.07 0.32 −0.66 1.58 2074b −1.62 0.48 −0.96 0.38 −0.66 1.58 2250a −2.15 0.21 −1.49 0.39 −0.66 1.58 1740a −1.62 0.49 −0.96 0.36 −0.66 1.58 81a 0.76 0.18 1.42 0.31 −0.66 1.58 1248b 0.18 0.52 0.85 0.18 −0.67 1.59 82b 0.44 0.58 1.10 0.26 −0.67 1.59 991b −1.16 0.56 −0.50 0.70 −0.67 1.59 1513b −2.06 0.40 −1.39 0.59 −0.67 1.59 992a −1.22 0.54 −0.55 0.71 −0.67 1.59 1147a −1.35 0.32 −0.68 0.29 −0.67 1.60 12a −1.59 0.21 −0.92 0.39 −0.67 1.60 2201a −1.89 0.24 −1.21 0.27 −0.68 1.60 1032d −0.81 0.78 −0.12 0.27 −0.69 1.61 1373a −2.37 0.22 −1.68 0.46 −0.69 1.61 2266b −1.26 0.33 −0.57 0.27 −0.69 1.61 795a −1.16 0.32 −0.47 0.19 −0.69 1.61 206a −1.93 0.37 −1.25 0.52 −0.69 1.61 1400a 1.27 0.78 1.96 0.47 −0.69 1.61 327f −0.25 0.63 0.44 0.23 −0.69 1.61 212a −1.81 0.33 −1.12 0.27 −0.69 1.61 2083e −1.73 0.39 −1.04 0.28 −0.69 1.61 555b 0.58 0.33 1.28 0.16 −0.69 1.62 1296a −2.22 0.41 −1.53 0.34 −0.69 1.62 226a −2.32 0.72 −1.63 0.44 −0.69 1.62 272d −2.17 0.22 −1.48 0.29 −0.69 1.62 1709a −2.13 0.40 −1.43 0.34 −0.70 1.62 1945a 4.78 0.43 5.47 0.28 −0.70 1.62 1631d 2.12 0.58 2.82 0.28 −0.70 1.62 1354a −2.29 0.66 −1.59 0.38 −0.70 1.62 24a −1.08 0.39 −0.38 0.35 −0.70 1.63 1284a −0.15 0.44 0.55 0.25 −0.71 1.63 184a −1.80 0.27 −1.09 0.35 −0.71 1.63 936b 1.54 0.58 2.25 0.17 −0.71 1.63 1a 4.14 0.55 4.85 0.50 −0.71 1.63 1677b 5.86 0.55 6.57 0.26 −0.71 1.64 747a −1.04 0.62 −0.33 0.21 −0.71 1.64 737a 0.67 0.46 1.38 0.48 −0.71 1.64 1953a −1.46 0.35 −0.74 0.75 −0.72 1.64 794a −0.98 0.85 −0.26 0.46 −0.72 1.65 2166a −1.84 0.39 −1.12 0.33 −0.73 1.65 1604a −2.12 0.49 −1.39 0.36 −0.73 1.66 479c −1.62 0.45 −0.89 0.24 −0.73 1.66 1245b −2.05 0.38 −1.32 0.56 −0.73 1.66 2040d −2.46 0.37 −1.73 0.23 −0.73 1.66 1502a −1.69 0.42 −0.95 0.38 −0.74 1.67 72a −0.51 0.39 0.24 0.35 −0.74 1.68 1917f −1.03 0.41 −0.28 0.44 −0.75 1.69 1650a −1.85 0.41 −1.09 0.40 −0.76 1.69 192a −1.83 0.41 −1.07 0.79 −0.76 1.69 1620a −1.99 0.27 −1.23 0.43 −0.76 1.69 1951a −1.81 0.32 −1.05 0.69 −0.76 1.70 1398a −2.82 0.45 −2.05 0.43 −0.77 1.70 2355c −1.79 0.48 −1.02 0.30 −0.77 1.70 1394b 1.65 0.77 2.42 0.24 −0.77 1.71 1651a −2.01 0.24 −1.24 0.66 −0.77 1.71 2071a −2.70 0.03 −1.93 0.28 −0.78 1.71 340a −2.01 0.24 −1.23 0.38 −0.78 1.72 368b −0.08 0.51 0.70 0.26 −0.78 1.72 736a 2.45 0.61 3.24 0.54 −0.79 1.73 64.2a 1.87 0.88 2.66 0.56 −0.79 1.73 17a 0.06 0.68 0.86 0.32 −0.80 1.74 1475a −1.53 0.33 −0.73 0.39 −0.80 1.74 2161c −1.79 0.44 −0.99 0.70 −0.80 1.74 143.2c 1.35 0.33 2.16 0.23 −0.81 1.75 1540a −1.64 0.43 −0.83 0.57 −0.81 1.76 1521b −1.05 0.59 −0.23 0.15 −0.82 1.76 2156c −2.35 0.36 −1.53 0.39 −0.82 1.76 2035d 0.44 0.71 1.26 0.43 −0.82 1.77 1618b 0.76 0.88 1.59 0.38 −0.82 1.77 1516a −2.38 0.36 −1.55 0.45 −0.83 1.78 1803a −1.30 0.55 −0.46 0.85 −0.83 1.78 1593b −2.07 0.66 −1.23 0.31 −0.84 1.79 1919a −1.03 0.43 −0.19 0.48 −0.84 1.79 1648a −2.08 0.43 −1.24 0.56 −0.84 1.79 2109a 3.09 0.81 3.94 0.81 −0.84 1.79 1241a −0.64 0.38 0.22 0.80 −0.86 1.82 392a 0.29 0.94 1.16 0.35 −0.86 1.82 1713a −2.09 0.40 −1.23 0.42 −0.86 1.82 144.2a 0.63 0.27 1.50 0.27 −0.86 1.82 2255a −1.13 0.35 −0.26 0.46 −0.87 1.83 1533a −2.04 0.70 −1.17 0.37 −0.87 1.83 690a −0.08 0.56 0.79 0.19 −0.87 1.83 1317a −2.69 0.92 −1.82 0.61 −0.88 1.83 2163a −1.44 0.74 −0.56 0.38 −0.88 1.84 979a 1.91 0.69 2.78 0.52 −0.88 1.84 1747a −2.25 0.79 −1.37 0.41 −0.88 1.84 507a −0.37 0.46 0.51 0.81 −0.88 1.84 890a −0.61 0.58 0.28 0.39 −0.88 1.85 1137b −0.71 1.21 0.18 0.36 −0.89 1.85 395a −2.00 0.46 −1.11 0.29 −0.89 1.85 51a −0.61 0.76 0.28 0.60 −0.89 1.85 1309b −2.56 0.05 −1.66 0.23 −0.90 1.86 1462a −0.23 0.28 0.68 0.39 −0.92 1.89 1708a −1.09 0.57 −0.17 0.85 −0.92 1.89 1086c −1.08 0.45 −0.16 0.74 −0.92 1.89 1313a −2.71 0.38 −1.78 0.33 −0.93 1.91 1439b −0.90 0.30 0.04 0.36 −0.94 1.91 153b −0.48 0.31 0.46 0.95 −0.94 1.92 1790a −2.28 0.33 −1.33 0.54 −0.95 1.93 961a −0.73 0.63 0.22 0.43 −0.95 1.93 493a 0.99 0.89 1.94 0.28 −0.96 1.94 1463a −0.08 0.21 0.88 0.17 −0.96 1.94 172a 2.00 0.43 2.97 0.35 −0.97 1.96 1454d −1.78 0.39 −0.80 0.21 −0.97 1.96 1143d −1.02 0.47 −0.05 0.52 −0.98 1.97 862c −1.96 1.22 −0.98 0.56 −0.98 1.97 766b −1.85 0.31 −0.86 0.50 −0.99 1.99 1412b 1.90 0.29 2.89 0.49 −0.99 1.99 1423b 3.55 0.77 4.54 0.20 −0.99 1.99 850a −0.14 0.42 0.87 0.59 −1.01 2.02 148a −0.73 0.40 0.32 0.27 −1.05 2.07 1696a 3.70 0.51 4.75 0.31 −1.05 2.07 1396b −2.51 0.36 −1.45 0.49 −1.06 2.08 2141a 1.46 0.40 2.53 0.64 −1.07 2.10 1503c −0.13 0.75 0.95 0.30 −1.08 2.11 639a −1.04 0.62 0.04 0.50 −1.08 2.12 1682a −0.59 0.32 0.50 0.38 −1.09 2.13 2153a −0.83 0.49 0.26 0.41 −1.09 2.13 2241a −0.24 0.39 0.86 0.48 −1.10 2.15 2263b −1.18 0.52 −0.08 0.42 −1.10 2.15 1438a 3.02 0.39 4.17 0.43 −1.15 2.22 2059b −1.36 0.47 −0.13 0.49 −1.22 2.34 1646a 1.35 0.79 2.58 0.51 −1.23 2.35 851d −1.81 0.47 −0.58 0.63 −1.23 2.35 465b −1.16 0.37 0.08 0.68 −1.25 2.37 990a 2.62 0.67 3.87 0.96 −1.25 2.38 1488b 0.21 0.78 1.46 0.66 −1.25 2.38 1452a 2.09 0.61 3.35 0.28 −1.26 2.40 1270a −1.47 0.36 −0.19 0.54 −1.28 2.43 2142a 0.23 0.57 1.52 1.18 −1.29 2.45 1371a −3.40 1.22 −2.10 0.45 −1.30 2.46 945a 0.76 0.68 2.06 0.30 −1.30 2.47 2117b 2.31 1.27 3.62 1.12 −1.31 2.48 1367a 0.92 0.83 2.25 0.65 −1.33 2.51 1818a 2.82 0.88 4.16 1.23 −1.34 2.53 2198b −0.03 0.54 1.32 1.21 −1.34 2.54 1139a 0.17 0.84 1.56 0.96 −1.39 2.61 851a −1.51 0.60 −0.13 0.40 −1.39 2.62 1138a 2.33 0.75 3.73 0.88 −1.41 2.65 1008a 2.72 0.80 4.14 0.92 −1.42 2.67 2113a 2.70 1.23 4.13 1.11 −1.43 2.69 552a 0.19 0.55 1.65 0.46 −1.46 2.74 2374a 0.73 0.76 2.21 0.60 −1.48 2.79 1532a −0.57 0.70 0.94 0.70 −1.51 2.85 2118a −0.83 0.68 0.69 0.38 −1.52 2.86 1366a 1.60 0.90 3.14 0.82 −1.53 2.90 1262b −0.27 0.47 1.28 1.13 −1.55 2.93 144.1c 2.31 0.40 4.24 0.49 −1.93 3.80 21a 0.69 0.77 2.95 0.77 −2.26 4.80 1246a 0.28 0.85 3.33 1.44 −3.05 8.29 1253a −1.26 0.64 2.10 1.84 −3.36 10.26 2224a 0.08 0.44 3.48 0.64 −3.40 10.57 1015d −1.04 0.52 3.01 1.83 −4.05 16.52 2252b −0.50 0.58 3.90 1.80 −4.39 21.00

TABLE 4 Normal Gene ID OA AVG STD AVG STD DIF(OA-N) Fold 1028c 1.81 0.75 0.24 0.94 1.57 2.96 768a 1.99 0.54 0.88 0.55 1.11 2.16 141c 3.94 0.57 3.01 0.75 0.93 1.90 1548c 5.49 0.41 4.79 0.46 0.69 1.62 1357a −2.01 0.12 −1.73 0.07 −0.28 1.21 168c 5.11 0.19 5.40 0.21 −0.29 1.22 383d −1.78 0.18 −1.47 0.14 −0.30 1.24 2127c 0.08 0.23 0.48 0.31 −0.39 1.31 530b 1.39 0.21 1.78 0.23 −0.40 1.32 1405c 3.41 0.34 3.81 0.16 −0.41 1.32 1765a −1.60 0.28 −1.19 0.28 −0.41 1.33 166a −0.97 0.34 −0.56 0.25 −0.41 1.33 1797a −1.79 0.25 −1.38 0.30 −0.42 1.33 1729a 3.95 0.37 4.37 0.23 −0.42 1.34 1857c −0.91 0.16 −0.49 0.20 −0.42 1.34 523a −1.36 0.28 −0.93 0.32 −0.43 1.34 2172c −2.54 0.17 −2.11 0.11 −0.43 1.35 58a −0.09 0.22 0.34 0.24 −0.43 1.35 244a −1.91 0.01 −1.47 0.12 −0.44 1.35 70d −1.65 0.30 −1.21 0.34 −0.44 1.36 1472a 0.07 0.40 0.51 0.23 −0.44 1.36 452a −0.80 0.33 −0.36 0.21 −0.45 1.36 1481c −1.53 0.19 −1.09 0.32 −0.45 1.36 1940e −0.44 0.30 0.01 0.20 −0.45 1.36 1930a −2.00 0.27 −1.54 0.37 −0.45 1.37 739a −0.46 0.27 0.00 0.15 −0.46 1.37 1612a −0.56 0.41 −0.09 0.28 −0.47 1.39 14a −0.93 0.24 −0.45 0.30 −0.47 1.39 1727a −1.68 0.31 −1.20 0.27 −0.48 1.39 1220b 2.96 0.46 3.44 0.15 −0.48 1.40 33a 1.31 0.22 1.80 0.35 −0.49 1.40 1146a 0.55 0.33 1.04 0.34 −0.50 1.41 1738b −1.57 0.25 −1.07 0.36 −0.50 1.41 810a −2.11 0.30 −1.61 0.28 −0.50 1.42 1993b −1.33 0.38 −0.82 0.34 −0.51 1.42 2147a −1.63 0.41 −1.11 0.33 −0.52 1.43 1678a 6.05 0.47 6.57 0.26 −0.52 1.44 56a 3.79 0.23 4.32 0.38 −0.53 1.44 1814c −1.03 0.40 −0.49 0.37 −0.54 1.45 129b 0.47 0.26 1.01 0.26 −0.54 1.45 1924a −0.46 0.34 0.08 0.41 −0.54 1.45 557b −1.56 0.24 −1.02 0.39 −0.54 1.45 1254a −0.48 0.46 0.06 0.28 −0.54 1.46 1292c −0.94 0.32 −0.40 0.47 −0.54 1.46 2221c −0.01 0.25 0.53 0.33 −0.54 1.46 490c 4.71 0.34 5.26 0.42 −0.54 1.46 907a −2.23 0.20 −1.68 0.29 −0.55 1.47 469d −0.61 0.31 −0.05 0.29 −0.56 1.47 713a −1.30 0.34 −0.74 0.25 −0.56 1.47 1372a 1.49 0.32 2.05 0.30 −0.56 1.47 482a −1.55 0.25 −0.99 0.39 −0.56 1.48 1098a −2.29 0.30 −1.72 0.31 −0.56 1.48 1785a −2.19 0.09 −1.63 0.27 −0.56 1.48 1624b −0.95 0.39 −0.38 0.36 −0.57 1.48 1441d −1.09 0.29 −0.52 0.50 −0.57 1.48 553b −0.76 0.16 −0.19 0.27 −0.57 1.48 2179a −2.12 0.29 −1.55 0.46 −0.57 1.49 1257b −0.76 0.22 −0.18 0.34 −0.58 1.49 1506d −1.45 0.32 −0.88 0.36 −0.58 1.49 1939c −2.37 0.07 −1.79 0.36 −0.58 1.49 2007a −1.93 0.29 −1.35 0.20 −0.58 1.49 13a −0.25 0.52 0.33 0.24 −0.58 1.50 1288a −1.12 0.25 −0.53 0.36 −0.58 1.50 1949a −1.40 0.25 −0.82 0.50 −0.59 1.50 142.2c 1.04 0.28 1.63 0.26 −0.59 1.50 1054a −0.73 0.26 −0.14 0.31 −0.59 1.50 1404c 2.76 0.43 3.35 0.29 −0.59 1.51 8a −0.51 0.51 0.08 0.30 −0.60 1.51 46a −0.07 0.54 0.52 0.34 −0.60 1.51 1985a −1.92 0.23 −1.33 0.50 −0.60 1.51 326e −0.12 0.25 0.48 0.24 −0.60 1.51 85.1c −0.04 0.40 0.56 0.22 −0.60 1.51 1675a −1.75 0.14 −1.15 0.40 −0.60 1.52 574a 0.54 0.26 1.14 0.47 −0.61 1.52 2159b −2.29 0.29 −1.67 0.44 −0.62 1.53 2108b 0.49 0.54 1.10 0.29 −0.62 1.54 45.1b 4.48 0.51 5.11 0.29 −0.62 1.54 2173a 2.84 0.40 3.47 0.49 −0.63 1.55 1676a −1.90 0.07 −1.27 0.47 −0.63 1.55 581a −1.77 0.16 −1.14 0.25 −0.63 1.55 1695a 0.22 0.30 0.85 0.59 −0.63 1.55 1414b −0.28 0.42 0.35 0.39 −0.64 1.55 151b 0.13 0.48 0.77 0.28 −0.64 1.55 112d 0.04 0.49 0.68 0.40 −0.64 1.56 461a −1.37 0.49 −0.73 0.24 −0.64 1.56 1615b −1.61 0.56 −0.97 0.34 −0.64 1.56 310h −1.41 0.50 −0.76 0.25 −0.64 1.56 297a −1.13 0.38 −0.48 0.25 −0.64 1.56 1801b −0.24 0.28 0.41 0.38 −0.65 1.56 23a −1.60 0.45 −0.96 0.22 −0.65 1.56 1739a −0.50 0.43 0.14 0.36 −0.65 1.57 170a 1.94 0.28 2.59 0.22 −0.65 1.57 1955a −1.57 0.30 −0.93 0.52 −0.65 1.57 2088a −0.75 0.46 −0.10 0.29 −0.65 1.57 2243b −2.44 0.24 −1.78 0.30 −0.65 1.57 1440a 1.14 0.42 1.79 0.36 −0.65 1.57 2351c −1.39 0.37 −0.74 0.32 −0.65 1.57 1415b −0.73 0.33 −0.07 0.32 −0.66 1.58 2074b −1.62 0.48 −0.96 0.38 −0.66 1.58 2250a −2.15 0.21 −1.49 0.39 −0.66 1.58 1740a −1.62 0.49 −0.96 0.36 −0.66 1.58 81a 0.76 0.18 1.42 0.31 −0.66 1.58 1248b 0.18 0.52 0.85 0.18 −0.67 1.59 82b 0.44 0.58 1.10 0.26 −0.67 1.59 1147a −1.35 0.32 −0.68 0.29 −0.67 1.60 12a −1.59 0.21 −0.92 0.39 −0.67 1.60 2201a −1.89 0.24 −1.21 0.27 −0.68 1.60 2266b −1.26 0.33 −0.57 0.27 −0.69 1.61 795a −1.16 0.32 −0.47 0.19 −0.69 1.61 206a −1.93 0.37 −1.25 0.52 −0.69 1.61 327f −0.25 0.63 0.44 0.23 −0.69 1.61 212a −1.81 0.33 −1.12 0.27 −0.69 1.61 2083e −1.73 0.39 −1.04 0.28 −0.69 1.61 555b 0.58 0.33 1.28 0.16 −0.69 1.62 1296a −2.22 0.41 −1.53 0.34 −0.69 1.62 272d −2.17 0.22 −1.48 0.29 −0.69 1.62 1709a −2.13 0.40 −1.43 0.34 −0.70 1.62 1945a 4.78 0.43 5.47 0.28 −0.70 1.62 1631d 2.12 0.58 2.82 0.28 −0.70 1.62 24a −1.08 0.39 −0.38 0.35 −0.70 1.63 1284a −0.15 0.44 0.55 0.25 −0.71 1.63 184a −1.80 0.27 −1.09 0.35 −0.71 1.63 936b 1.54 0.58 2.25 0.17 −0.71 1.63 1a 4.14 0.55 4.85 0.50 −0.71 1.63 1677b 5.86 0.55 6.57 0.26 −0.71 1.64 747a −1.04 0.62 −0.33 0.21 −0.71 1.64 737a 0.67 0.46 1.38 0.48 −0.71 1.64 2166a −1.84 0.39 −1.12 0.33 −0.73 1.65 479c −1.62 0.45 −0.89 0.24 −0.73 1.66 2040d −2.46 0.37 −1.73 0.23 −0.73 1.66 1502a −1.69 0.42 −0.95 0.38 −0.74 1.67 72a −0.51 0.39 0.24 0.35 −0.74 1.68 1917f −1.03 0.41 −0.28 0.44 −0.75 1.69 1650a −1.85 0.41 −1.09 0.40 −0.76 1.69 1620a −1.99 0.27 −1.23 0.43 −0.76 1.69 1951a −1.81 0.32 −1.05 0.69 −0.76 1.70 2355c −1.79 0.48 −1.02 0.30 −0.77 1.70 1394b 1.65 0.77 2.42 0.24 −0.77 1.71 2071a −2.70 0.03 −1.93 0.28 −0.78 1.71 340a −2.01 0.24 −1.23 0.38 −0.78 1.72 368b −0.08 0.51 0.70 0.26 −0.78 1.72 736a 2.45 0.61 3.24 0.54 −0.79 1.73 17a 0.06 0.68 0.86 0.32 −0.80 1.74 1475a −1.53 0.33 −0.73 0.39 −0.80 1.74 143.2c 1.35 0.33 2.16 0.23 −0.81 1.75 1540a −1.64 0.43 −0.83 0.57 −0.81 1.76 1521b −1.05 0.59 −0.23 0.15 −0.82 1.76 2156c −2.35 0.36 −1.53 0.39 −0.82 1.76 2035d 0.44 0.71 1.26 0.43 −0.82 1.77 1919a −1.03 0.43 −0.19 0.48 −0.84 1.79 1648a −2.08 0.43 −1.24 0.56 −0.84 1.79 1241a −0.64 0.38 0.22 0.80 −0.86 1.82 1713a −2.09 0.40 −1.23 0.42 −0.86 1.82 144.2a 0.63 0.27 1.50 0.27 −0.86 1.82 2255a −1.13 0.35 −0.26 0.46 −0.87 1.83 690a −0.08 0.56 0.79 0.19 −0.87 1.83 2163a −1.44 0.74 −0.56 0.38 −0.88 1.84 979a 1.91 0.69 2.78 0.52 −0.88 1.84 1747a −2.25 0.79 −1.37 0.41 −0.88 1.84 507a −0.37 0.46 0.51 0.81 −0.88 1.84 890a −0.61 0.58 0.28 0.39 −0.88 1.85 395a −2.00 0.46 −1.11 0.29 −0.89 1.85 1309b −2.56 0.05 −1.66 0.23 −0.90 1.86 1462a −0.23 0.28 0.68 0.39 −0.92 1.89 1086c −1.08 0.45 −0.16 0.74 −0.92 1.89 1313a −2.71 0.38 −1.78 0.33 −0.93 1.91 1439b −0.90 0.30 0.04 0.36 −0.94 1.91 153b −0.48 0.31 0.46 0.95 −0.94 1.92 1790a −2.28 0.33 −1.33 0.54 −0.95 1.93 961a −0.73 0.63 0.22 0.43 −0.95 1.93 493a 0.99 0.89 1.94 0.28 −0.96 1.94 1463a −0.08 0.21 0.88 0.17 −0.96 1.94 172a 2.00 0.43 2.97 0.35 −0.97 1.96 1454d −1.78 0.39 −0.80 0.21 −0.97 1.96 1143d −1.02 0.47 −0.05 0.52 −0.98 1.97 766b −1.85 0.31 −0.86 0.50 −0.99 1.99 1412b 1.90 0.29 2.89 0.49 −0.99 1.99 1423b 3.55 0.77 4.54 0.20 −0.99 1.99 850a −0.14 0.42 0.87 0.59 −1.01 2.02 148a −0.73 0.40 0.32 0.27 −1.05 2.07 1696a 3.70 0.51 4.75 0.31 −1.05 2.07 1396b −2.51 0.36 −1.45 0.49 −1.06 2.08 2141a 1.46 0.40 2.53 0.64 −1.07 2.10 1503c −0.13 0.75 0.95 0.30 −1.08 2.11 639a −1.04 0.62 0.04 0.50 −1.08 2.12 1682a −0.59 0.32 0.50 0.38 −1.09 2.13 2153a −0.83 0.49 0.26 0.41 −1.09 2.13 2241a −0.24 0.39 0.86 0.48 −1.10 2.15 2263b −1.18 0.52 −0.08 0.42 −1.10 2.15 1438a 3.02 0.39 4.17 0.43 −1.15 2.22 2059b −1.36 0.47 −0.13 0.49 −1.22 2.34 1646a 1.35 0.79 2.58 0.51 −1.23 2.35 851d −1.81 0.47 −0.58 0.63 −1.23 2.35 465b −1.16 0.37 0.08 0.68 −1.25 2.37 990a 2.62 0.67 3.87 0.96 −1.25 2.38 1488b 0.21 0.78 1.46 0.66 −1.25 2.38 1452a 2.09 0.61 3.35 0.28 −1.26 2.40 1270a −1.47 0.36 −0.19 0.54 −1.28 2.43 2142a 0.23 0.57 1.52 1.18 −1.29 2.45 945a 0.76 0.68 2.06 0.30 −1.30 2.47 1367a 0.92 0.83 2.25 0.65 −1.33 2.51 2198b −0.03 0.54 1.32 1.21 −1.34 2.54 1139a 0.17 0.84 1.56 0.96 −1.39 2.61 1138a 2.33 0.75 3.73 0.88 −1.41 2.65 1008a 2.72 0.80 4.14 0.92 −1.42 2.67 552a 0.19 0.55 1.65 0.46 −1.46 2.74 2374a 0.73 0.76 2.21 0.60 −1.48 2.79 1532a −0.57 0.70 0.94 0.70 −1.51 2.85 2118a −0.83 0.68 0.69 0.38 −1.52 2.86 1366a 1.60 0.90 3.14 0.82 −1.53 2.90 1262b −0.27 0.47 1.28 1.13 −1.55 2.93 144.1c 2.31 0.40 4.24 0.49 −1.93 3.80 21a 0.69 0.77 2.95 0.77 −2.26 4.80 1246a 0.28 0.85 3.33 1.44 −3.05 8.29 1253a −1.26 0.64 2.10 1.84 −3.36 10.26 2224a 0.08 0.44 3.48 0.64 −3.40 10.57 1015d −1.04 0.52 3.01 1.83 −4.05 16.52 2252b −0.50 0.58 3.90 1.80 −4.39 21.00

The use of differential display to isolate gene transcripts has enabled the present inventors to develop a microarray chip enriched in transcripts involved in osteoarthritis. The use of this chip to analyze samples from canines with osteoarthritis (1) confirms the results from differential display and (2) enables further characterization of canine osteoarthritis at the molecular level. Transcripts analyzed by qPCR (discussed infra) have validated the differential expression analysis from the microarray.

EXAMPLE 5 Quantitative Polymerase Chain Reaction (qPCR)

Confirmation of changes in RNA transcripts was performed using quantitative PCR. Reverse transcriptase reactions were performed using Super Script™ II Reverse Transcriptase for RT-PCR (Invitrogen) according to the manufacture's directions. 1 g of RNA was added to 1.5 μL10 mM dNTP's, 1.5 μL random hexamers and 0.6 μL Oligo dT primers and brought to a final volume of 15 uL. Samples were incubated at 68° C. for 10 minutes and then brought down to 4° C. for at least 1 minute using a GeneAmp PCR System 9700 (Applied Biosystems). A portion (0.25×) of the above reaction was removed and used as a minus RT reaction (Negative Control containing No Super Script II Reverse Transcriptase). Using the same Super Scrip™ II Reverse Transcriptase kit, a master mix containing 3 μL of 10×RT buffer, 6 μL of 25 mM MgCl₂, 3 μL 0.1M DTT and 1.5 μL RNAse Inhibitor was made. A portion (0.25×) was removed and 0.375 μL H₂O was added for the minus RT samples. To the remainder of the Master Mix, 1.125 μL Super Scrip™ II Reverse Transcriptase was added for the positive RT reactions. All reactions were then incubated at 42° C. for 1 hour, boiled at 95° C. for 5 minutes, and the brought down to 4° C. using a GeneAmp PCR System 9700. The samples were then diluted 1 part RT reaction to 29 Parts H₂O to create a stock of cDNA for experimentation.

Primers and 5′ nuclease assay probes were designed based on selected sequences from the differential display using Primer Express™ v1.5 (Applied Biosystems Primer Express® Tutorial for Real Time Quantitative PCR Primer and Probe Design Tutorial). Minor groove Binding probes (ABI Custom Oligo Synthesis Factory) were ordered from ABI. All oligos were reconstituted with TE buffer pH=8.0 (Ambion) to 100 μM stock concentration, and then diluted with TE buffer to a 5 μM working stock concentration. TaqMan® Universal PCR Master Mix (Applied Biosystems) was used for quantitative PCR reactions according to the manufacture's directions. Primer concentration was 300 μM each and Probe concentration was 200 μM (determined optimal from earlier experiments). 4 μl of RT and minus RT reactions were used for quantitative PCR reactions. All positive reactions were done in triplicate, and negative controls were performed singly. Standard qPCR conditions were used as described in the TaqMan® Universal Master Mix (Applied Biosystems, 50.0° C. for 2 minutes, 95.0° C. for 10 minutes, and 40-50 cycles of 95° C. for 15 seconds then 60° C. for 1 minute) at 0.5 volumes. Samples were run on an ABI Prism 7700 Sequence Detector using ABI Sequence Detector Program v1.7a.

All samples were run singularly against each primer/probe set to determine what standard curve should be used. Standard curves were generated using serial dilutions of liver RNA or RNA from experimental samples. Alternately, if the samples did not fall within either of the curve ranges, the sample with the lowest C_(T) (cycle threshold) would be re-reverse transcribed and a 1:10 serial dilution would be used as the standard curve for that primer/probe set. Values were normalized to G3PDH (glyceraldehyde-3-phoshate dehydrogenase) levels as determined by quantitative PCR. Inductions were calculated from each of the lowest sample's normalized value. Error bars represent standard error of the means.

Table 5 shows the primers and probes used for the qPCR analysis.

TABLE 5 SEQ I. Clone ID Target NO: Primers and Probes (5′-3′) K9 G3PDH- 1567 GTC ATC ATC TCT GCT CCT TCT GC Fwd Rev 1568 TGA CAA TCT TGA GGG AGT TGT CA Probe 1569 6FAM-CTT CTC ATG GTT CAC GCC CAT CAC AAA-MGBNFQ 11B-Fwd 1570 TTG ATA CTC CTA GTC TTG TCT ATT CAC TGA Rev 1571 TCG AGT TTT TGC TCT TTG GAG AA Probe 1572 6FAM-TCA TTC AAC CCA GCA TTG AAC AAG GCT-MGBNFQ 59A-Fwd 1573 AGC AGG TGT TCA TCC CAG AAT G Rev 1574 GGG TGT GAC GCA CCA ACA G Probe 1575 6FAM-CCT ACA GCC AGG TGC AGT GTC ACA GC-MGBNFQ 127B-Fwd 1576 GCA TCC CCG AGC CTC AT Rev 1577 GGG TGC TAT ACA GTC CAG GTC AA Probe 1578 6FAM-TCT ATC TCC CCA GCT GCT TCC CCA C-MGBNFQ 141C-Fwd 1579 AAG GAA GTC CAA TAA ATT CTT TGT TTG Rev 1580 TGC CAG GAT TGT TGG TCT GTT Probe 1581 6FAM-CTC CTG CTG TTA CCC CAG TGA AGA GTG TTT T-MGBNFQ 159A-Fwd 1582 CAG GCT GCC AAC GAA TGG Rev 1583 AGA CCG GCT CTT GAG GAC AGA Probe 1584 6FAM-TGG CCT GCC TGA CAA GTA CTG AGC TTC-MGBNFQ 768A-Fwd 1585 CCA TCT TTT CTC CCT CCT CAA CT Rev 1586 GGT CTT CAG GTG ATG GTG GG Probe 1587 6FAM-TCT TCA GCG GGA CTC CCT CTT GGG-MGBNFQ 794A-Fwd 1588 AGT TTG GCT CCC TAA GTA GAT CAC TT Rev 1589 GAA TAC AGC TAC CAC CAA CTT TCA ATT Probe 1590 6FAM-CTA AAT GCT TTG GAT GAT TGT CCG CTT CTC A-MGBNFQ 851D-Fwd 1591 TGA ACA TGC TAA CCT GCG TCT C Rev 1592 GAC GTG TTT TCT CGG CTG GA Probe 1593 6FAM-CCC ACG TAG TCC GTG GGA GAC CC-MGBNFQ 2252B-Fwd 1594 CAT GTT GGT TCT GAA AAG GTC TGA Rev 1595 GGT GAG CCA AAA GCC ATA GCT Probe 1596 6FAM-CCT TTA CTC CGT GCA GAT CTA CTG CTC AGC-MGBNFQ 2258A-Fwd 1597 TGT GTT TTG TTT GTT TTG CTT GTT T Rev 1598 AGA AAG AAA AAA GGA AAG ATG AGT TCA Probe 1599 6FAM-CGC CCC CCA AAC CTT TTG TTC TCT C-MGBNFQ 1678A-Fwd 1600 ACT ATT TCA TAC CCT CTC CCA CTA CAA Rev 1601 CCC ACA AAT ACA ATT TAT ATT TAG CAG TGA Probe 1602 6FAM-TTT CCG TGC AGT TAC CTT TCA TTT TTA AAG CAA-MGBNFQ 1466B-Fwd 1603 ACA AGA CAT CCT ACC GCT GGT T Rev 1604 CAG CTC AGG ACC CTC GTA GAA Probe 1605 6FAM-CTG CAG CAT CGG CCC CAA GTG-MGBNFQ 2141A-Fwd 1606 TGA GAT TCA ACA CTT CCC AGT CAA Rev 1607 TGT CCC CAT GGT TAG GTG ACA Probe 1608 6FAM-TAT TTA CAT CAG GCA AAG CAG CAT CAG CAA-MGBNFQ 2267A-Fwd 1609 AAA TAA CAA AAG GTG AAA CTT CTA TAC AAA TAT T Rev 1610 AAG TTT GTA AGA CAC TTA AAC TCT TTC TGC Probe 1611 6FAM-CCA AAA ATT CTT TAC TCA GTC ACA CAA CAA ATG AGG-MGBNFQ

EXAMPLE 6 qPCR Analysis of Canine OA Cartilage

qPCR was performed as described, supra, on 6 osteoarthritic cartilage samples from clinically diagnosed canines undergoing total hip replacement and 8 normal cartilage samples. Results are shown in FIG. 2 (A-E).

EXAMPLE 7 Microarray Analysis of Treated OA Samples

A. In Vitro Chondrocyte Cell Culture

Canine cartilage was digested in a 37° C. shaking water bath using the following enzymes: trypsin (0.25%) for 25 minutes, hyaluronidase (150 U/ml) for 1 hour, and collagenase (0.78%) overnight. Digested cartilage was filtered to obtain chondrocytes. Dulbecco's Modified Eagle Medium (DMEM)+2.4% alginate (low melting)+ cells were dropped from a 10 cc syringe into calcium chloride (102 mM) to form “beads.” Chondrocyte beads were cultured in DMEM/F12+P/S (100 U/mL penicillin and 100 μg/mL streptomycin)+10% Fetal Bovine Serum (FBS). Media was changed every other day. At the end of the treatment (see below), the chondrocyte beads were dissolved in sodium citrate (55 mM) and EDTA (30 mM). Suspensions were centrifuged at 1800 rpm for 10 minutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion® RNAqueous™) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at −20° C. until RNA isolation could be performed.

B. RNA Isolation from Cell Culture

Samples were vortexed and homogenized using a Quiashredder (Qiagen) column according to manufacture's directions. The homogenized lysate was collected and 1 equal volume of 64% ethanol was added to it. This mixture was then applied to an RNAqueous™ filter cartridge, 700 uL at a time, and centrifuged for 1 minute at 10,000 rpm. The cartridge was washed using 700 uL wash solution #1 and 500 uL wash solution #⅔ with centrifugation at 10,000 rpm for 1 minute for each wash. The filter cartridge was dried by centrifugation (10,000 rpm) for 1 minute. RNA was eluted 3 times by centrifugation (as above) using 30 uL aliquots of 95-100° C. elution solution. The resulting RNA was DNAse-treated and quantitated as stated previously. Following RNA isolation, the RNA was prepared for microarray hybridization as stated previously.

C. Statistical Analysis of Cell Culture Microarray

Data were transformed to logarithm, base 2. Data were normalized using quantile normalization. After normalization, a concordance correlation was computed.

Differentially expressed genes were determined using a paired t test (α=0.05) for the EPA vs. AA; EPAstim vs. AAstim; chondroitin sulfate and glucosamine 100 μg vs. control, 100 μg vs. 10 μg and 10 μg vs. control.

Differentially expressed genes were determined by first using ratios of AAstim vs. AA and EPAstim vs. EPA followed by a paired t test (α=0.05) for the ratios of AAstim/AA and EPAstim/EPA.

Differentially expressed genes following a unidirectional trend for all glucosamine and chondroitin sulfate analyses were determined for each treatment pair where responses to the treatment resulted in increases or decreases, in the same direction, in all three samples.

Differentially expressed genes were determined using a Welch modified two-sample t test for both 1,25 D3 vs. control and 24,25 D3 vs. control (α=0.05).

1. Chondroitin Sulfate Treatment

Chondrocytes were treated with chondroitin sulfate based on the recognition of chondroitin sulfate as a joint nutrient. Chondrocyte beads were treated with 100 μg/mL, 10 μg/mL or 0 μg/mL (control) chondroitin sulfate (n=3) for 1 week in DMEM/F12+P/S+10% FBS. Media was changed every other day. After one week, the chondrocytes beads were dissolved in sodium citrate (55 mM) and EDTA (30 mM). Suspensions were centrifuged at 1800 rpm for 10 minutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion® RNAqueous™) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at −20° C. until RNA isolation could be performed. One sample from the chondroitin sulfate treatment was removed due to poor correlation with the rest of the array data. This reduced this analysis to an n=3. The results are shown in Tables 7-12.

TABLE 7 Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 100 μg/mL and 10 μg/mL Chondroitin Sulfate on Chondrocytes (p < 0.5) Gene ID DIF (100-10) Fold 1071b −0.21 1.15 1089d 0.23 1.17 1221a −0.19 1.14 1228a −0.44 1.36 1263b −0.22 1.16 1304a −0.14 1.10 143.2c 0.22 1.16 1477a −0.22 1.17 1576a −0.30 1.23 1577a −0.12 1.09 158a −0.23 1.17 1717a −0.29 1.22 1732a −0.10 1.07 1747a −0.16 1.12 1749a −0.49 1.40 1752a −0.30 1.23 1917f −0.43 1.35 2173a −0.63 1.54 2267a −0.55 1.47 2374a −0.54 1.46 322a −0.41 1.33 368b −0.17 1.12 392a −0.07 1.05 508 −0.17 1.12 639a −0.26 1.20 711a −0.24 1.18 720a −0.17 1.12 73b −0.24 1.18 753b −0.26 1.20 831a −0.38 1.30 91f −0.27 1.21 936b −0.21 1.16 997a 0.15 1.11

TABLE 8 Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 100 μg/mL and 0 μg/mL Chondroitin Sulfate (Control) on Chondrocytes (p < 0.5) Gene ID DIF (100-Control) Fold 1044c 0.19 1.14 1136b −0.32 1.25 1137b −0.20 1.15 1212b −0.31 1.24 1248b −0.24 1.18 1254a 0.13 1.09 1304a −0.35 1.28 143.2c 0.28 1.21 1450a −0.12 1.09 1457b 0.10 1.07 1524a 0.24 1.18 159a 0.84 1.79 1741a −0.42 1.34 1801b 0.26 1.20 1880a −0.75 1.68 1911b −0.24 1.18 1930a −0.34 1.27 297a −0.31 1.24 398b −0.34 1.27 466b −0.38 1.30 487a −0.21 1.16 538a −0.25 1.19 713a −0.20 1.15 720a −0.21 1.16 739a −0.29 1.22 795a −0.43 1.35 831a −0.18 1.13 85.2b −0.25 1.19 961a −0.31 1.24 995a −0.60 1.52 999a −0.35 1.27

TABLE 9 Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 10 μg/mL and 0 μg/mL Chondroitin Sulfate (Control) on Chondrocytes (p < 0.5) Gene ID DIF (10-Control) Fold 1050a −0.27 1.21 1097c −0.35 1.27 1163d 0.18 1.13 1366a −0.12 1.09 1406a 0.13 1.10 145b 0.35 1.28 1554c −0.73 1.66 170a 0.20 1.15 1764a −0.11 1.08 1911b −0.29 1.23 2088a −0.13 1.10 2105a 0.23 1.17 2205a −0.27 1.20 2266b −0.16 1.12 33a 0.38 1.31 406a-r −0.02 1.01 708a 0.13 1.10 768a 0.81 1.75 840d-r −0.19 1.14 93e 0.14 1.10

TABLE 10 Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 100 μg/mL and 10 μg/mL Chondroitin Sulfate on Chondrocytes; Dataset shows a Unidirectional Trend in Fold Change Across All Samples Gene ID DIF (100-10) Fold 491 1.21 2.32 498 0.18 1.13 508 −0.17 1.12 1016b 0.36 1.28 1044c 0.33 1.26 1089d 0.23 1.17 1091b 0.18 1.13 1106a −0.25 1.19 111a −0.11 1.08 1129a −0.22 1.17 1133b −0.12 1.09 1137b 0.20 1.15 11b 0.69 1.61 1212b −0.24 1.18 1217a −0.34 1.27 1221a −0.19 1.14 1225b −0.23 1.17 1228a −0.44 1.36 1254a 0.15 1.11 1263b −0.22 1.16 127b 0.31 1.24 128a −0.43 1.35 129b 0.26 1.20 1304a −0.14 1.10 132a −0.35 1.27 1364d 0.29 1.22 1403a −0.25 1.19 1406a −0.14 1.11 1409b −0.22 1.17 1416a −0.33 1.25 142.1c −0.11 1.08 142.2c 0.76 1.70 143.2c 0.22 1.16 144.1c 0.82 1.77 1453a −0.13 1.09 1477a −0.22 1.17 1489a −0.18 1.14 1519a 0.42 1.34 1532a 0.22 1.16 154a 0.04 1.03 1577a −0.12 1.09 158a −0.23 1.17 159a 0.90 1.87 1612a −0.13 1.10 1629a −0.17 1.13 163a −0.27 1.20 1646a −0.06 1.04 1693b −0.08 1.06 1705a −0.34 1.26 1717a −0.29 1.22 1732a −0.10 1.07 1739a −0.05 1.03 173a −0.48 1.40 1741a −0.21 1.16 1747a −0.16 1.12 1749a −0.49 1.40 1752a −0.30 1.23 1760c −0.09 1.07 1772a −0.36 1.28 186a 0.27 1.21 1874b −0.18 1.13 1880a −0.40 1.32 1881b −0.11 1.08 1892a 0.24 1.18 1945a −0.07 1.05 1989b −0.02 1.02 1990a −0.37 1.29 2002c −0.16 1.12 2008a −0.05 1.03 2013a 0.05 1.04 2023b −0.17 1.12 2047b −0.17 1.13 2083e −0.28 1.21 2095a −0.48 1.40 2102a −0.64 1.56 2108b −0.13 1.09 2109a −0.41 1.33 2117b −0.37 1.29 211b 0.40 1.32 2148a 0.10 1.07 2173a −0.63 1.54 2182b 0.26 1.20 2205a 0.34 1.27 2221c 0.21 1.16 2223a −0.22 1.17 2267a −0.55 1.47 2374a −0.54 1.46 27a −0.14 1.10 297a −0.17 1.12 307b 0.15 1.11 309a 0.42 1.34 322a −0.41 1.33 106a 0.15 1.11 106a 0.18 1.13 368b −0.17 1.12 379a −0.15 1.11 392a −0.07 1.05 410c −0.22 1.17 425c −0.25 1.19 455c −0.01 1.01 468f −0.19 1.14 472a −0.46 1.38 483a 0.15 1.11 545a −0.12 1.08 553b 0.38 1.31 596e −0.10 1.07 60a −0.40 1.32 623a 0.64 1.56 639a −0.26 1.20 63a −0.25 1.19 67a −0.56 1.47 704b −0.39 1.31 711a −0.24 1.18 713a −0.26 1.20 718a −0.18 1.14 720a −0.17 1.12 736a −1.16 2.23 737a −0.22 1.16 73b −0.24 1.18 753b −0.26 1.20 759b −0.28 1.21 795a −0.19 1.14 812d-r −0.19 1.14 831a −0.38 1.30 833a −0.28 1.22 84.2c −0.33 1.26 840d-r 0.28 1.22 841b −0.31 1.24 847a −0.18 1.13 87.2b −0.41 1.33 878c −0.25 1.19 8a −0.21 1.16 90c −0.25 1.19 91f −0.27 1.21 929a −0.72 1.64 936b −0.21 1.16 93e −0.30 1.23 945a −0.27 1.20 990a −0.19 1.14 995a −0.35 1.27 999a −0.12 1.09

TABLE 11 Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 100 μg/mL and 0 μg/mL (Control) Chondroitin Sulfate on Chondrocytes; Dataset shows a Unidirectional Trend in Fold Change Across All Samples Gene ID DIF (100-Control) Fold 1002b −0.18 1.13 1026b −0.11 1.08 1044c 0.19 1.14 106a 0.13 1.10 1133b −0.20 1.15 1136b −0.32 1.25 1137b −0.20 1.15 1138a −0.32 1.25 1159b 0.17 1.12 1183a 0.18 1.13 1189a 0.12 1.09 11b 1.14 2.20 1212b −0.31 1.24 1217a −0.45 1.37 1228a −0.34 1.26 1240a −0.03 1.02 1246a −0.04 1.03 1248b −0.24 1.18 1254a 0.13 1.09 1294b 0.40 1.32 1304a −0.35 1.28 1366a −0.26 1.19 136b −0.41 1.33 1394b −0.19 1.14 1403a −0.28 1.21 1405c −0.02 1.02 1409b −0.15 1.11 141c 0.58 1.50 142.2c 1.01 2.02 1423b −0.12 1.09 143.2c 0.28 1.21 1450a −0.12 1.09 1456b −0.09 1.06 146b 0.27 1.21 1472a 0.16 1.12 1477a −0.45 1.37 1489a −0.37 1.29 1519a 0.18 1.13 154a −0.11 1.08 156b 0.35 1.27 158a −0.27 1.21 159a 0.84 1.79 15b −0.29 1.22 1612a −0.34 1.27 1630b −0.24 1.18 1631d −0.26 1.20 1632a −0.23 1.17 163a −0.40 1.32 1695a 0.05 1.03 1705a −0.46 1.37 1715a −0.14 1.10 1717a −0.24 1.18 1732a −0.10 1.07 1734b −0.27 1.21 1740a −0.07 1.05 1741a −0.42 1.34 1747a −0.10 1.07 1749a −0.36 1.28 1752a −0.26 1.20 1758a −0.21 1.16 1772a −0.06 1.05 1811b −0.19 1.14 1813b −0.13 1.10 1874b −0.36 1.29 1911b −0.24 1.18 1917f −0.41 1.33 1928a −0.16 1.12 1930a −0.34 1.27 1945a −0.26 1.20 1948b 0.14 1.10 2013a −0.17 1.12 2035d −0.30 1.24 2047b −0.22 1.17 205a −0.29 1.22 2088a −0.18 1.14 2129a −0.17 1.12 2136b 0.23 1.17 2154a −0.21 1.16 2266b −0.18 1.14 2267a −0.55 1.47 2374a −0.54 1.45 297a −0.31 1.24 319b −0.39 1.31 322a −0.36 1.28 32e 0.19 1.14 33a 0.20 1.15 106a 0.32 1.25 106a 0.15 1.11 392a −0.15 1.11 398b −0.34 1.27 401a −0.20 1.15 406a-r −0.03 1.02 421a −0.19 1.14 425c −0.36 1.28 44a −0.18 1.13 472a −0.29 1.22 487a −0.21 1.16 50.2d −0.25 1.19 538a −0.25 1.19 553b 0.28 1.21 568a −0.15 1.11 57a −0.18 1.13 596e −0.17 1.13 59a 0.39 1.31 60a −0.30 1.23 616a −0.19 1.14 61c −0.14 1.10 639a −0.26 1.20 63a −0.18 1.13 6b 0.18 1.13 713a −0.20 1.15 720a −0.21 1.16 72a −0.22 1.17 736a −0.71 1.63 739a −0.29 1.22 749a −0.24 1.18 794a −0.12 1.08 795a −0.43 1.35 828a −0.49 1.40 82b 0.21 1.16 831a −0.18 1.13 833a −0.26 1.20 84.1b −0.10 1.07 84.2c −0.35 1.28 844c-r −0.09 1.06 85.2b −0.25 1.19 890a −0.08 1.06 91f −0.15 1.11 936b −0.15 1.11 953a −0.04 1.03 961a −0.31 1.24 995a −0.60 1.52 996a −0.08 1.06 999a −0.35 1.27

TABLE 12 Differential Expression of OA-Associated Genes with Chondroitin Sulfate Treatment Comparing the Effect of 10 μg/mL and 0 μg/mL (Control) Chondroitin Sulfate on Chondrocytes; Dataset shows a Unidirectional Trend in Fold Change Across All Samples Gene ID DIF (10-C) Fold 491 −1.37 2.59 493 −0.05 1.04 498 −0.35 1.27 1016b −0.50 1.42 1050a −0.27 1.21 1072a −0.48 1.40 1089d −0.21 1.15 1105a −0.40 1.32 1136b −0.32 1.25 1137b −0.39 1.31 1139a −0.07 1.05 1145a −0.11 1.08 1174d −0.45 1.36 1217a −0.11 1.08 1247a −0.20 1.15 1304a −0.21 1.15 131a −0.21 1.16 1366a −0.12 1.09 1406a 0.13 1.10 1409b 0.07 1.05 1411a −0.18 1.13 145b 0.35 1.28 1500b −0.24 1.18 1521b −0.19 1.14 154a −0.15 1.11 1632a −0.20 1.15 1656a 0.16 1.12 1721a −0.19 1.14 1739a 0.07 1.05 173a 0.37 1.29 1741a −0.21 1.16 1747a 0.07 1.05 1758a −0.19 1.14 1764a −0.11 1.08 1772a 0.29 1.22 1811b −0.16 1.12 1852a 0.38 1.30 1892a −0.35 1.28 1895b 0.06 1.04 1908a −0.12 1.09 1930a −0.22 1.16 1945a −0.19 1.14 1948b 0.19 1.14 2013a −0.22 1.17 2088a −0.13 1.10 2105a 0.23 1.17 2109a 0.68 1.61 2149d −0.14 1.10 2205a −0.27 1.20 2266b −0.16 1.12 307b −0.14 1.10 319b −0.11 1.08 326e 0.22 1.17 32e 0.18 1.14 33a 0.38 1.31 348c 0.15 1.11 379a 0.21 1.16 406a-r −0.02 1.01 413a −0.17 1.12 421a −0.13 1.10 472a 0.17 1.13 489c 0.04 1.03 530b −0.24 1.18 538a −0.48 1.39 56a 0.06 1.04 57a −0.22 1.17 583e −0.22 1.17 64.2a −0.24 1.18 704b 0.23 1.17 708a 0.13 1.10 719a −0.35 1.28 737a 0.11 1.08 749a −0.29 1.23 753b 0.21 1.15 75c 0.24 1.19 795a −0.25 1.19 828a −0.65 1.57 831a 0.20 1.15 840d-r −0.19 1.14 848a 0.09 1.07 87.2b 0.42 1.34 90c 0.27 1.20 91f 0.13 1.09 93e 0.14 1.10 945a 0.26 1.20 961a −0.31 1.24 98d 0.15 1.11 995a −0.25 1.19 999a −0.23 1.17

2. Glucosamine Treatment

Glucosamine treatment was used to determine the effect of this joint health nutrient on the differential expression of OA-associated genes. Chondrocyte beads were treated with 100 μg/mL, 10 μg/mL or 0 μg/mL (control) glucosamine (n=3) for 1 week in DMEM/F12+P/S+10% FBS. Media was changed every other day. After one week, the chondrocytes beads were dissolved in sodium citrate (55 mM) and EDTA (30 mM). Suspensions were centrifuged at 1800 rpm for 10 minutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion® RNAqueous™) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at −20° C. until RNA isolation could be performed. The results are shown in Tables 13-18.

TABLE 13 Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 100 μg/mL and 10 μg/mL Glucosamine on Chondrocytes (p < 0.5) Gene ID DIF (100-10) Fold 1044c −1.12 2.17 10c −0.48 1.39 1131b −0.80 1.74 1183a −0.43 1.34 1257b 0.46 1.38 1479a −0.49 1.41 1532a 0.34 1.27 1656a −0.73 1.66 170a −0.56 1.47 1896b −0.59 1.51 2085c −0.44 1.36 2137b −0.67 1.59 322a 0.41 1.32 687a −0.46 1.38 695a −0.51 1.42 841b 0.79 1.73

TABLE 14 Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 100 μg/mL and 0 μg/mL (Control) Glucosamine on Chondrocytes (p < 0.5) Gene ID DIF (100-C) Fold 1413b −1.73 3.31 1892a 0.94 1.92

TABLE 15 Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 10 μg/mL and 0 μg/mL (Control) Glucosamine on Chondrocytes (p < 0.5) Gene ID DIF (10-C) Fold 1294b −0.55 1.46 1364d −0.67 1.59 1384a 1.61 3.04 150a 1.23 2.34 151b 1.18 2.27 1645a 0.43 1.34 2100b −0.34 1.26 2198b 0.76 1.70 2210a −0.51 1.43 38a −0.57 1.48 457c −1.57 2.96 464b −0.34 1.27 623a −0.56 1.47 63a 0.20 1.15 794a −0.24 1.18

TABLE 16 Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 100 μg/mL and 10 μg/mL Glucosamine on Chondrocytes; Dataset shows a Unidirectional Trend in Fold Change Across All Samples Gene ID DIF (100-10) Fold 508 −0.41 1.33 1004a −0.68 1.60 1023c −0.58 1.49 1026b −0.52 1.43 1030a −0.70 1.63 1044c −1.12 2.17 1089d −0.42 1.34 1094b −0.35 1.28 1099c −0.66 1.58 10c −0.48 1.39 1104b −0.79 1.73 1110b −0.59 1.50 1131b −0.80 1.74 1159b −0.86 1.81 1183a −0.43 1.34 1227b −1.55 2.94 131a −0.70 1.62 1405c −0.40 1.32 1406a −0.58 1.49 1423b −0.73 1.66 1437a −0.55 1.47 1479a −0.49 1.41 1500b −0.97 1.95 150a −0.72 1.64 1584a −0.80 1.74 1594a −1.04 2.05 159a 0.56 1.48 1626c −0.82 1.77 1639a −0.58 1.50 1656a −0.73 1.66 1669d −0.69 1.61 1670d −1.20 2.30 1849d −0.54 1.45 1895b −0.22 1.16 1896b −0.59 1.51 2085c −0.44 1.36 2092c −0.52 1.43 2104a −0.67 1.59 2117b −1.00 1.99 2137b −0.67 1.59 2167a −0.83 1.77 2267a −1.12 2.18 260c −0.63 1.55 370a 0.24 1.18 413a −0.40 1.32 421a −0.58 1.49 48b −0.89 1.85 687a −0.46 1.38 695a −0.51 1.42 706b −0.39 1.31 720a −0.42 1.34 847a −0.50 1.41 863c-r −0.45 1.36 87.2b −0.87 1.83 906a −0.36 1.28 981a −0.70 1.62

TABLE 17 Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 100 μg/mL and 0 μg/mL (Control) Glucosamine on Chondrocytes; Dataset shows a Unidirectional Trend in Fold Change Across All Samples Gene ID DIF (100-C) Fold 491 0.56 1.47 1026b −0.30 1.23 1030a −0.50 1.41 1040b −0.63 1.55 106a 0.23 1.17 1094b −0.14 1.10 111a −0.85 1.81 1227b −1.15 2.23 1413b −1.73 3.31 146b −0.57 1.49 1500b −1.51 2.85 158a −1.07 2.10 1630b −1.23 2.34 1669d −0.24 1.19 1670d −0.26 1.20 2048a −0.27 1.20 2331c −0.74 1.67 283a −0.69 1.62 370a 0.15 1.11 375d −0.22 1.16 384c −0.39 1.31

TABLE 18 Differential Expression of OA-Associated Genes with Glucosamine Treatment Comparing the Effect of 10 μg/mL and 0 μg/mL (Control) Glucosamine on Chondrocytes; Dataset shows a Unidirectional Trend in Fold Change Across All Samples Gene ID DIF (10-Control) Fold 1006b −0.79 1.73 104a −0.53 1.44 106a 0.24 1.18 1072a 0.52 1.44 1089d 0.63 1.54 111a −0.29 1.22 104a −0.20 1.15 1190b −0.52 1.43 130b 0.35 1.28 1364d −0.67 1.59 1384a 1.61 3.04 1400a −0.66 1.58 1405c 0.66 1.58 1437a 0.56 1.47 1466b −0.75 1.68 146b −0.27 1.20 1469a 0.57 1.48 150a 1.23 2.34 151b 1.18 2.27 1554c −0.34 1.27 1631d 0.48 1.39 1645a 0.43 1.34 1670d 0.94 1.92 1683a −1.36 2.57 1712a 0.18 1.14 1948b 0.25 1.19 1a −1.05 2.07 2095a −0.94 1.92 2117b 1.14 2.20 262c −0.18 1.14 27a 0.10 1.07 283a −0.32 1.25 421a 0.55 1.46 45.1b 0.15 1.11 457c −1.57 2.96 459a −0.40 1.32 468f 0.34 1.27 483a −0.37 1.29 489c 0.22 1.16 490c 0.17 1.13 50.2d 0.30 1.23 52a −1.14 2.20 530b −0.24 1.18 553b 0.26 1.20 557b −0.17 1.13 63a 0.20 1.15 795a 0.28 1.21 986a −0.61 1.52 98d 0.17 1.13 996a 0.77 1.71

3. 1α,25-dihydroxyvitamin D₃ (1,25 D3) and 24R,25-dihydroxyvitamin D₃ (24,25 D3) Treatment

1,25 D3 and 24R,25D3 treatment was applied to chondrocytes based on their known effects on prostaglandin production and differential responses to the vitamin D3 metabolites in chondrocytes to determine the effect of these compounds on OA-associated gene expression. Chondrocyte beads were treated with 10⁻⁷M 1,25 D3 or 10⁻⁷M 24,25 D3 for 24 hours or without Vitamin D (equivalent ethanol was added to control), (n=3) in DMEM/F12+P/S+10% FBS. After 24 hours, the chondrocyte beads were dissolved in sodium citrate (55 mM) and EDTA (30 mM). Suspensions were centrifuged at 1800 rpm for 10 minutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion® RNAqueous™) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at −20° C. until RNA isolation could be performed. The results are shown in Tables 19 and 20.

TABLE 19 Differential Expression of OA-Associated Genes with 1α,25- dihydroxyvitamin D₃ Treatment on Chondrocytes (p < 0.5) Gene ID median C median 1,25 vD3 DIF (1,25-Control) Fold 1023c 10.95 10.12 −0.83 1.77 1042a 11.30 10.86 −0.44 1.36 1068a 9.62 8.89 −0.73 1.66 1096a 9.68 9.36 −0.32 1.25 1101a 7.76 7.16 −0.60 1.51 1103a 7.92 7.29 −0.63 1.55 1120a 8.17 7.77 −0.40 1.32 1147a 8.04 7.43 −0.61 1.52 117.1d 8.60 8.16 −0.44 1.35 1174d 9.66 8.30 −1.36 2.57 1178a 8.12 7.55 −0.57 1.49 1275c 8.72 8.07 −0.64 1.56 1304a 8.92 8.07 −0.85 1.80 1447a 9.67 9.21 −0.46 1.37 1461a 7.89 6.96 −0.92 1.90 1503c 8.86 8.47 −0.40 1.32 1521b 9.79 8.50 −1.29 2.44 153b 8.49 8.03 −0.46 1.37 1554c 9.09 8.49 −0.61 1.52 1576a 8.27 7.66 −0.61 1.52 1582a 8.10 7.62 −0.47 1.39 1592a 8.03 7.35 −0.67 1.59 1601a 7.68 7.30 −0.38 1.30 1612a 10.11 8.71 −1.40 2.64 1779b 7.63 7.09 −0.54 1.45 1813b 11.20 10.19 −1.01 2.02 1849d 11.81 11.31 −0.49 1.41 185a 7.61 7.28 −0.34 1.26 1863c 10.52 9.95 −0.57 1.49 1889a 8.20 7.45 −0.75 1.68 1892a 9.71 8.90 −0.81 1.75 1920a 8.24 7.54 −0.70 1.62 192a 7.84 7.61 −0.23 1.17 1943a 7.71 7.35 −0.36 1.28 1991d 9.36 8.48 −0.88 1.84 2109a 10.56 11.72 1.16 2.23 2117b 9.27 11.06 1.79 3.46 2163a 8.69 7.49 −1.20 2.30 2179a 7.71 7.17 −0.54 1.45 2198b 9.71 8.36 −1.35 2.54 2201a 8.19 7.74 −0.45 1.37 2223a 15.42 14.58 −0.84 1.79 2263b 8.85 8.11 −0.74 1.67 2266b 8.69 7.92 −0.77 1.71 2337a 13.57 12.62 −0.95 1.93 234a 7.95 7.61 −0.33 1.26 2353a 8.43 7.96 −0.47 1.38 299a 7.62 7.90 0.29 1.22 106a 16.00 15.99 −0.01 1.00 367a 10.83 10.22 −0.61 1.52 388a 7.81 7.52 −0.29 1.22 415b 7.86 7.33 −0.53 1.44 478a 9.24 8.85 −0.38 1.30 5b 10.21 9.71 −0.51 1.42 61c 10.58 9.88 −0.70 1.62 719a 10.62 10.27 −0.35 1.27 721b 9.08 8.62 −0.46 1.38

TABLE 20 Differential Expression of OA-Associated Genes with 24R,25- dihydroxyvitamin D₃ Treatment on Chondrocytes (p < 0.5) Gene ID median C median 24,25 vD3 DIF (24,25-Control) Fold 1023c 11.11 10.48 −0.64 1.56 1068a 9.68 9.21 −0.47 1.39 1098a 7.01 8.18 1.17 2.25 1285a 7.37 7.69 0.33 1.25 1335b 7.85 7.69 −0.16 1.12 1474a 6.94 7.70 0.76 1.69 1481c 7.70 7.39 −0.31 1.24 1592a 8.09 7.46 −0.63 1.55 16b 8.47 7.73 −0.74 1.67 1726a 7.88 7.37 −0.50 1.42 1779b 7.66 7.32 −0.35 1.27 2330b 8.01 7.74 −0.27 1.21 340a 7.71 8.41 0.69 1.62 371a 9.33 9.60 0.26 1.20 401a-r 7.17 7.55 0.39 1.31 449a 7.29 7.59 0.30 1.23 70d 7.88 8.23 0.35 1.28 725a 7.42 8.23 0.81 1.75 832a 8.37 9.04 0.67 1.59 996a 14.73 14.52 −0.22 1.16

4. Eicosapentaenoic acid (EPA) and Arachidonic Acid (AA) Treatment

Chondrocytes were treated with eicosapentaenoic acid (EPA) and arachidonic acid (AA) based on the recognition in the literature that EPA acts as an anti-inflammatory. AA was used as a control to represent a typical western diet. Chondrocytes were enriched with 50 μM EPA or 50 μM AA (using albumin as a carrier) for two weeks in DMEM/HAMS+P/S+10% FBS. Media was changed every other day. Each set (n=3) was split and half were treated with stimulated monocyte neutrophil conditioned media (SMNCM) for one week with media changed every other day. SMNCM was made by isolating monocytes and neutrophils from canine whole blood using NycoPrep™ according to the manufacture's directions. Monocytes and neutrophils were stimulated with lipopolysaccharide (20 ng/mL) for 72 hours. The resulting supernatant was used as SMNCM in cell culture experimentation (SMNCM made up 10% of media used during experimentation). Chondrocyte beads were dissolved in sodium citrate (55 mM) and EDTA (30 mM). Suspensions were centrifuged at 1800 rpm for 10 minutes. Cells were washed with phosphate buffer and centrifuged again at 1800 rpm for 5 minutes. One mL lysis binding solution (Ambion® RNAqueous™) was added to the isolated canine chondrocyte pellet, mixed thoroughly and stored at −20° C. until RNA isolation could be performed. One sample from the EPA/AA stim treatment was removed due to poor correlation with the rest of the array data. This reduced these analyses to an n=3. The results are shown in Tables 21-23.

TABLE 21 Differential Expression of OA-Associated Genes Comparing AA Treatment with EPA Treatment of Chondrocytes (p < 0.05) Gene ID DIF (AA-EPA) Fold 1190b 0.42 1.34 1381a −0.12 1.08 1391a 0.26 1.20 1450a −0.64 1.56 1451a −0.85 1.80 1466b 0.33 1.26 1678a −0.67 1.60 1730a 0.45 1.36 2095a −0.35 1.28 493 −0.46 1.38 708a 0.51 1.43 99b −0.17 1.13

TABLE 22 Differential Expression of OA- Associated Genes with Inflammatory Stimulation Comparing AA Treatment with EPA Treatment of Chondrocytes (p < 0.05) Gene ID DIF (AAs-EPAs) Fold 1099c 1.12 2.17 1104b 0.73 1.66 1106a 0.46 1.38 1184a 0.54 1.45 1190b 0.56 1.47 128a −0.68 1.60 1323b-r −0.58 1.50 1339b −1.58 2.98 1391a 0.88 1.84 1425a 0.68 1.61 1459c −0.38 1.30 154a −1.27 2.42 1576a −0.33 1.26 1629a −0.58 1.49 1639a 0.64 1.56 164c −0.69 1.61 166a −0.43 1.35 1752a −0.27 1.20 2035d −0.57 1.48 2113a −0.90 1.86 2120a-r 0.28 1.22 35c −0.19 1.14 65.2a −0.86 1.82 90c −0.61 1.53

TABLE 23 Differential Expression of OA-Associated Genes with Inflammatory Stimulation Comparing EPA Treatment and AA Treatment of Chondrocytes (p < 0.05) DIF Gene ID AAs-AA EPAs-EPA ((AAs-AA) − (EPAs-EPA)) Fold 517 0.10 1.08 −0.98 1.97 1007a −2.37 −2.00 −0.37 1.29 1030a 0.25 −0.23 0.48 1.39 1042a 0.89 0.51 0.38 1.30 104a 0.10 0.95 −0.85 1.80 1091b 1.20 0.90 0.30 1.23 1145a −0.41 −0.55 0.14 1.10 1184a 1.48 0.94 0.55 1.46 1227b 1.47 1.13 0.35 1.27 1270a 0.19 −1.04 1.23 2.35 1339b −1.91 0.09 −2.00 4.00 134b 0.83 0.16 0.66 1.58 1381a −1.65 −2.22 0.56 1.47 1406a 0.46 0.09 0.37 1.29 1469a 0.77 1.36 −0.59 1.51 1549a 0.13 0.15 −0.02 1.01 154a 2.97 4.48 −1.51 2.85 1585b 0.28 −0.21 0.49 1.40 1598a 0.19 −0.09 0.27 1.21 1656a 1.28 0.36 0.92 1.89 1659a 0.19 0.03 0.16 1.12 1670d 1.52 0.68 0.84 1.79 1678a −1.27 −1.76 0.49 1.40 1741a 0.02 −0.64 0.66 1.58 1895b 0.89 0.42 0.46 1.38 1929c 0.35 0.23 0.12 1.09 1930a 0.59 0.34 0.25 1.19 1981a −0.04 −0.30 0.27 1.21 2008a 0.44 0.03 0.41 1.33 2255a 0.16 −0.08 0.25 1.19 253b −0.18 0.19 −0.37 1.29 342a 0.02 0.13 −0.11 1.08 350b −0.79 0.09 −0.87 1.83 364a 0.20 0.28 −0.08 1.06 384c 0.13 −0.19 0.31 1.24 465b −0.13 −0.84 0.71 1.64 490c −0.45 0.09 −0.54 1.45 516c 0.04 1.09 −1.05 2.07 687a 1.16 0.74 0.42 1.34 706b 0.70 −0.44 1.14 2.20 709a 0.53 0.09 0.44 1.36 758b 0.09 −0.18 0.27 1.21 89c 0.55 1.25 −0.70 1.62 981a 1.11 0.52 0.59 1.51

The experiments demonstrated that various treatments can affect the expression of OA-associated genes. In some cases, the effect on gene expression was statistically significant (p<0.05). In other cases, although the change could not be demonstrated to be statistically significant due to the variability of expression, there was a definite trend for expression to be changed in one direction only (either increased expression or decreased expression). This unidirectional change is considered to be both biologically relevant and significant. In some cases, it is believed that down-regulation of expression of certain genes will have a beneficial biological effect on OA. For other genes, increased expression will have a beneficial biological effect. The invention allows the identification of genes that correlate with beneficial effects as demonstrated by regulation of compounds known to be involved in anti-inflammatory processes, for example. The invention also permits the identification of new compounds which should have beneficial effects based on their regulation of gene expression of the OA-associated genes described in this invention.

The results demonstrate that one can affect the biology of the cells with various treatments and have a direct impact on gene expression of OA-associated genes. The invention permits the rapid and powerful screening of compounds to identify candidate treatments and preventatives of OA in animals, particularly humans.

The disclosures of each patent, patent application, publication and accession number to database sequences cited or described in this document are hereby incorporated herein by reference, in their entirety.

Various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. 

What is claimed:
 1. A method to diagnose a canine subject who exhibits signs of osteoarthritis, the method comprising: a) obtaining a cartilage sample from the canine subject; b) measuring in the sample the amount of a transcription product comprising SEQ ID NO:217, wherein the measuring comprises hybridizing one or more probes capable of specifically hybridizing to the transcription product, wherein the probes comprise at least 10 nucleic acids, and wherein the probes are identical to or are fully complementary to a corresponding region of the transcription product to which they specifically hybridize and the corresponding region distinguishes the transcription product from any other transcription product in the sample; c) determining if the transcription product comprising SEQ ID NO:217 measured in step b) is down regulated in comparison to a non-osteoarthritis cartilage sample; and d) diagnosing the canine as having osteoarthritis when SEQ ID NO: 217 is down regulated in comparison to a non-osteoarthritis cartilage sample.
 2. The method of claim 1, wherein: step b) further comprises measuring in the sample the amount of at least one other transcription product produced by the expression of one or more genes known to be differentially expressed in an osteoarthritis cartilage sample as compared with a non-osteoarthritis cartilage sample, the transcription product comprising any of SEQ ID NOs: 1-216 and 218-1558; step c) further comprises determining if the transcription product measured in step b) is differentially expressed in comparison to a non-osteoarthritis cartilage sample; and step d) comprises making a diagnosis or prognosis of osteoarthritis in the canine based upon whether indications of osteoarthritis are present given the determination of step c).
 3. The method of claim 2, wherein the differential expression in comparison to a non-osteoarthritis cartilage sample is at least 1.5 fold.
 4. The method of claim 2, wherein the one or more probes is a collection of 50 or more probes.
 5. The method of claim 2, wherein the one or more probes is a collection of 200 or more probes.
 6. The method of claim 2, wherein the transcription product comprises any of SEQ ID NOs:1-216 or 218-396.
 7. The method of claim 2, wherein the transcription product comprises any of SEQ ID NOs:1-216 [217].
 8. The method of claim 2, wherein, if the transcription product is up-regulated in comparison to a non-osteoarthritis cartilage sample, it is selected from the group consisting of SEQ ID NOs: 1-4; and if the transcription product is down-regulated in comparison to a non-osteoarthritis cartilage sample, it is selected from the group consisting of SEQ ID NOs: 5-216. 